Carnitine

Carnitine is a water-soluble antioxidant derived mostly from the human diet. Some sources include fish, meat, poultry, and dairy products. It is formed from the biosynthesis of lysine and methionine. Carnitine is found in nearly all cells of the body and is essential in sperm energy production by transporting long-chain fatty acids from the cytosol into the mitochondria. In addition, carnitine is involved in the removal of cytotoxic compounds from the cell. Normally, the body produces a sufficient amount of carnitine to meet daily needs; however, in some cases individuals are incapable of producing enough. For instance, vegetarians were found to be significantly deficient in carnitine as opposed to an omnivorous control group [47].

Carnitine is also important with respect to many properties specific to sperm maturation. In a meta-analysis by Ross et al., oral supplementation with carnitine improved spermatozoa motility in three out of four randomized controlled studies [48], Intra- and extracellular carnitine may be essential in sperm energy metabolism, and thereby provide the fuel for posttesticular processes involved in sperm motility. Motile spermatozoa have been found to have a greater degree of carnitine acetylation than immotile spermatozoa [49]. Moreover, free-l-carnitine is acety-lated only in mature spermatozoa [50]. Studies have suggested that the initiation of acquiring sperm motility occurs parallel to an increase in carnitine concentration in the epididymal lumen and acetyl-l-carnitine in spermatozoa [49, 50]. Carnitine that accumulates in the epididymis, in both free and acetylated forms, is utilized by spermatozoa for mitochondrial P-oxidation of long-chain fatty acids, as well as for enhancing the cellular energetic in mitochondria. This is done by facilitating the entry and utilization of fatty acids and restoring the phospholipid composition of its membrane by decreasing fatty acid oxidation. The resulting increase in metabolic rate allows for a greater production of energy and increased sperm motility. Table 22.1 summarizes the most recent studies on carnitine supplementation for improving sperm quality.

Table 22.1 Quality assessment of oral carnitine supplementation References Study design Cases

Costa et al. [51] Cross-sectional 100

Vitali et al. [52] Case-control 47

Lenzi et al. [53] Double-blind, placebo- 86

controlled, crossover

Cavallini et al. [54] Double-blind, random- 195 (39A; 44B; 47c) ized controlled

Dosage

Duration

Ages Main outcome

Placebo® therapy/placebo + 2-m wash-out + 2-m placebo/therapy + 2-m wash-out

LC (2 g/day) + LAC 6-m intervention + 3-m 27-40 (1 g/day)4; LC (2 g/ follow-up day) + LAC (1 g/ day) + Cinnoxicam (30 mg/4 day)®; Placebo0

t Motility (p <0.001) f Rapid linear progression (p <0.001) \ Mean velocity (p<0.001) \ Linearity index (p<0.001) \ Total number (p<0.001) t Motility (80%) t Total motility4 8

(p = 0.05) \ Concentration4® (p = 0.01) t Linearity4® (p = 0.03) t Motility4® (p <0.05) f Concentration4®

Balercia et al. [56]

Double-blind, randomized controlled

Double-blind, randomized, controlled

Double-blind, randomized controlled

LC (2 g/day) + LAC (1 g/ 2-m wash-out+ 6-m day)A; Placebo8 intervention + 2-m follow-up

20-40

LC (3 g/day)A; LAC (3 ¿/day)8; LC (2 g/ day) + LAC (1 g/day)c Placebo13

1-m wash-out+ 6-m intervention + 3-m follow-up

24-38

24-w intervention

18-65

t Total motility4

{p< 0.05) f Forward motility4

(p< 0.05) f Concentration48

{p< 0.05) f Forward motility4®0 {p< 0.05) t Morphology4

{p< 0.05) t TAC4-®'C (p<0.05) J, Motility4® {p> 0.05) t Total motility4 ® (p>0.05)

LC L-carnitine; LAC L-acetyl-carnitine; m month; w week; TAC total antioxidant capacity aGroup A had significantly higher pregnancy rate compared with group C (p<0.01), and group B had a significantly increased pregnancy rate compared with group A (p<0.05)

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