L-carnitine is an amino acid that was first isolated from beef muscle in 1905. Meat and milk are the most significant dietary sources of exogenous carnitine for humans. Approximately 75% of the body stores of L-carnitine are derived from the diet, where as only 25% are synthesized from lysine and methionine.

L-carnitine is concentrated in high energy demanding tissues such as skeletal and cardiac muscles and in a specialized reproductive tract organ such as the epididymis. In fact, it was reported that the concentration of L-carnitine in epididymal plasma and spermatozoa is nearly 2000-fold greater than circulating levels.

In epididymis, free L-carnitine is taken up from the blood plasma and is transported into the Epididymal fluid. It is then passively diffused into the spermatozoa, where it accumulates as both free and acetylated L-carnitine. The initiation of sperm motility occurs in parallel with the increase in concentration of free L-carnitine in the epididymal lumen.

As carnitine is necessary for transport of fatty acids into the mitochondria, low levels of carnitine reduce fatty acid concentrations within the mitochondria, leading to decrease energy production and potential alterations in sperm motility.

Low carnitine levels have been frequently reported in different studies in infertile men, that may suggest direct correlation of carnitine level with fertility

Below is a summary of few clinical studies showing the relationship between L-carnitine supplementation and semen quality.

1.     CLINICAL: PLACEBO-CONTROLLED, DOUBLE-BLIND, CROSSOVER TRIAL

The aim of this Placebo-controlled, double-blind, crossover trial was to determine the efficacy of L-carnitine therapy in selected cases of male infertility. One hundred infertile patients, with the following baseline sperm selection criteria: Concentration, 10-20 x 10(6) /mL; Total motility 10%-30%; Forward motility <15%; Atypical forms <70%; Velocity 10-30 micro/s; Linearity <4. Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, two months of therapy/placebo, two months of washout, and two months placebo/therapy. It has been found that L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels.

Reference: Lenzi A, Lombardo F, Sgro P, et al. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril 2003; 79:292-300. 59.

2.     CLINICAL

The aim of the study is to evaluate any possible effect of L-carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres. One hundred patients received 3 g d-1 of oral L-carnitine for 4 months. Sperm parameters were studied before, during and after this treatment. The results of the study indicate that L-carnitine can increase spermatozoal motility, both in a quantitative and in a qualitative manner. An increase in spermatozoal output was also observed (total number of ejaculated spermatozoa increased). The authors conclude that oral administration of L-carnitine may improve sperm quality at least in patients with idiopathic asthenozoospermia.

Reference: Costa M, et al. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994; 26:155- 159

3.     CLINICAL

This study was conducted to assay the effect of L-carnitine on sperm parameters in patients who needs intracytoplasmic sperm injection (ICSI) as a method for infertility treatment. The study population consisted of 65 men presenting with primary infertility due to idiopathic oligoasthenoteratozoospermia. L-carnitine was prescribed one gram orally every 8 hours for three months. Before and after the ending of the L-carnitine treatment, semen analysis was performed.

Results: The proportion of patients who had motile and grade C sperms rose significantly after treatment. In approximately 22%, complete asthenozoospermia changed to relative asthenozoospermia. Workers concluded that appearing motile sperms will potentially improve the technique of ICSI. The magnitude of the elevation in normal morphology is not clinically obvious, but it seems that it can be important in obtaining normal-shaped sperms for ICSI.

Reference: Afsaneh Khademi, et al. The effect of L-carnitine on sperm parameters in patients’ candidate for Intracytoplasmic Sperm Injection. Iranian Journal of Reproductive Medicine Vol. 2. No.2 pp:65-69, 2004 65

4.     CLINICAL

The aim of this study was to test the hypothesis that the free L-carnitine helps in maintaining normal fertility. A total of 61 adult males were categorized as fertile and infertile based on history and semen analysis. The result showed that infertile subjects had significantly lower when compared to fertile subjects with lowest concentration in azoospermic group. The results suggested that Carnitine level in seminal plasma plays an essential role in maintaining male fertility.

Reference: Syed D. Haseen et al. Role of L-carnitine in male infertility. J Pak Med Assoc, Vol. 61, No. 8, August 2011

5.     CLINICAL

Seminal plasma of 72 infertile men and 80 men with proved fertility as a control group was investigated and L-carnitine level was determined. Authors found that the concentration of L-carnitine was significantly lower in the infertile group compared with control group (80.59±56.43 mg/l versus 108.43±42.26 mg/l; P= 0.0009). There was also a statistically significant positive correlation between seminal plasma L-carnitine concentration, total sperm count, and the percentage of motile sperm (P= 0.0009, and P= 0.0000, respectively).

These finding suggest that the determination of seminal plasma L-carnitine level may be a useful test in evaluation of male infertility.

Reference: Sheikh N. et al. L-Carnitine Level in Seminal Plasma of Fertile and Infertile Men J Res Health Sci, Vol 7, No 1, pp. 43-48, 2007

EPIDIDYMIS

The epididymis (ep·i·did·y·mis) is the duct that conveys sperm from the testicle to the vas deferens (vas de·fe·rens). The epididymis is a highly coiled tube measuring 5-6 meters if unwound fully. and plays an important role in maintaining a physiological environment in the epididymal canal suitable for sperm maturation. Namely, sperm develops the capability of motility and fertilization (post testicular maturation) only when they pass through epididymis (Spermatozoa are non-motile and cannot fertilize an ovum after formation in the seminiferous tubules).