Advertisement

Drugs in R & D

, Volume 6, Issue 1, pp 1–9 | Cite as

Correlation between Seminal Carnitine and Functional Spermatozoal Characteristics in Men with Semen Dysfunction of Various Origins

  • Michele De Rosa
  • Bartolomeo Boggia
  • Biagio Amalfi
  • Stefano Zarrilli
  • Angela Vita
  • Annamaria Colao
  • Gaetano Lombardi
Original Research Article

Abstract

Background and objective: L-carnitine is an essential molecule involved in mitochondrial metabolism, controlling the transport of acetyl and acyl groups across the mitochondrial inner membrane. Carnitine and acetylated carnitine (L-acetylcarnitine) are found in high concentrations in the epididymis, where they also act as antioxidants, protecting spermatozoa against damage caused by reactive oxygen species. In this open study we investigated the correlation between seminal carnitine levels and spermatozoal function, and the effect of combined L-carnitine + L-acetylcarnitine therapy, in infertile men.

Patients and methods: 170 infertile men were enrolled in this study. Patients were divided into those with a total sperm motility below the normal WHO range (<50% motility, group 1 [n = 102]) and those with total sperm motility within the normal range (>=50% motility, group 2 [n = 68]). Patients in group 1 were further divided into two groups: those with primary or secondary azoospermia (1B [n = 36]), and those without (1A [n = 66]). Patients in group 1A received L-carnitine 1 g/day and L-acetylcarnitine 500mg twice daily for 6 months. Seminal carnitine levels were measured and correlated with sperm count and motility, eosin test, hypo-osmotic swelling test, acridine orange test for sperm nuclear DNA integrity and sperm kinetics evaluated by computer-assisted sperm analysis in all patients.

Results: There was a significant correlation between seminal carnitine concentration and sperm concentration, total sperm count, sperm total motility, rapid forward progression, live sperm count, membrane function, nuclear DNA integrity, capacity for cervical mucus penetration, linearity of spermatic movement, and amplitude of lateral sperm head movement (all p < 0.0001) in the entire study population. In group 1A, there was a significant increase in total motility, live sperm count, membrane integrity and linearity of spermatic movement after 3 and 6 months of L-carnitine/L-acetylcarnitine treatment, and in capacity for cervical mucus penetration after 6 months of treatment, compared with baseline.

Conclusion: Seminal carnitine concentration may be an appropriate marker of sperm and epididymal function. L-carnitine/L-acetylcarnitine treatment may be an effective therapy to improve mainly functional seminal parameters.

Keywords

Carnitine Epididymal Spermatozoon Free Carnitine Carnitine Level Total Sperm Count 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We acknowledge the excellent technical assistance provided by Mr Angelo Di Francia. This study had no funding and the authors have no conflicts of interest directly relevant to the content of this study.

References

  1. 1.
    Li B, Lloyd ML, Gudjonsson H, et al. The effect of enteral carnitine administration in humans. Am J Clin Nutr 1992; 55: 838–45PubMedGoogle Scholar
  2. 2.
    Casillas ER. Accumulation of carnitine by bovine spermatozoa during maturation in the epididymis. J Biol Chem 1973; 248: 8227–32PubMedGoogle Scholar
  3. 3.
    Casillas ER, Chaipayungpan S. The distribution of carnitine and acetylcarnitine in the rabbit epididymis and the carnitine content of rabbit spermatozoa during maturation. J Reprod Fertil 1979; 56: 439–44PubMedCrossRefGoogle Scholar
  4. 4.
    Casillas ER, Erickson BJ. Studies on carnitine synthesis in the rat epididymis. J Reprod Fertil 1975; 44: 287–91PubMedCrossRefGoogle Scholar
  5. 5.
    Hinton BT, Snoswell AM, Setchell BP. The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals. J Reprod Fertil 1979; 56: 105–11PubMedCrossRefGoogle Scholar
  6. 6.
    Marquis NR, Fritz IB. Effects of testosterone on the distribution of carnitine, acetylcarnitine, and carnitine acetyltransferase in tissues of the reproductive system of the male rat. J Biol Chem 1965; 240: 2197–200PubMedGoogle Scholar
  7. 7.
    Lenzi A, Lombardo F, Gandini L, et al. Metabolism and action of L-carnitine: its possible role in sperm tail function [in Italian]. Arch Ital Urol Nefrol Androl 1992; 64: 187–96PubMedGoogle Scholar
  8. 8.
    Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update 1996; 2: 87–102PubMedCrossRefGoogle Scholar
  9. 9.
    Marquis NR, Fritz IB. Enzymological determination of free carnitine concentrations in rat tissues. J Lipid Res 1964; 41: 184–7Google Scholar
  10. 10.
    Matalliotakis I, Koumantaki Y, Evageliou A, et al. L-carnitine levels in the seminal plasma of fertile and infertile men: correlation with sperm quality. Int J Fertil Womens Med 2000; 45: 236–40PubMedGoogle Scholar
  11. 11.
    Golan R, Weissenberg R, Lewin LM. Carnitine and acetylcarnitine in motile and immotile human spermatozoa. Int J Androl 1984; 7: 484–94PubMedCrossRefGoogle Scholar
  12. 12.
    Soffer Y, Shalev DP, Weissenberg R, et al. Survey of carnitine content of human semen using a semiquantitative auxanographic method: decreased semen total carnitine concentration in patients with azoospermia or severe oligozoospermia. Andrologia 1981; 13: 440–4PubMedCrossRefGoogle Scholar
  13. 13.
    Lewin LM, Shalev DP, Weissenberg R, et al. Carnitine and acylcarnitines in semen from azoospermic patients. Fertil Steril 1981; 36: 214–8PubMedGoogle Scholar
  14. 14.
    Eigenmann J, Bandhauer K, Tomamichel G. Seminal carnitine concentration in obstructive azoospermia. Eur Urol 1994; 26: 134–6PubMedGoogle Scholar
  15. 15.
    Casillas ER, Erickson BJ. The role of carnitine in spermatozoan metabolism: substrate-induced elevations in the acetylation state of carnitine and coenzyme A in bovine and monkey spermatozoa. Biol Reprod 1975; 12: 275–83PubMedCrossRefGoogle Scholar
  16. 16.
    Brooks DE, Hamilton DW, Mallek AH. Carnitine and glycerylphosphorylcholine in the reproductive tract of the male rat. J Reprod Fertil 1974; 36: 141–60PubMedCrossRefGoogle Scholar
  17. 17.
    Hamilton DW, Olson GE. Effects of carnitine on oxygen uptake and utilization of (U-14C)palmitate by ejaculated bull spermatozoa. J Reprod Fertil 1976; 46: 195–202PubMedCrossRefGoogle Scholar
  18. 18.
    Hartree EF, Mann T. Plasmalogen in ram semen, and its role in sperm metabolism. Biochem J 1959; 71: 423–34PubMedGoogle Scholar
  19. 19.
    Hartree EF, Mann T. Phospholipids in ram semen: metabolism of plasmalogen and fatty acids. Biochem J 1961; 80: 464–76PubMedGoogle Scholar
  20. 20.
    Brooks DE, Mann T. Pyruvate metabolism in boar spermatozoa. J Reprod Fertil 1973; 34: 105–19PubMedCrossRefGoogle Scholar
  21. 21.
    Johansen L, Bohmer T. Motility related to the presence of carnitine/acetylcarnitine in human spermatozoa. Int J Androl 1979; 2: 202–10CrossRefGoogle Scholar
  22. 22.
    Wolf G. Recent research on carnitine: its relation to lipid metabolism. Cambridge (MA): MIT Press, 1965Google Scholar
  23. 23.
    Vicari E, La Vignera S, Calogero AE. Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds. Fertil Steril 2002; 78: 1203–8PubMedCrossRefGoogle Scholar
  24. 24.
    Costa M, Canale D, Filicori M, et al. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994; 26: 155–9PubMedCrossRefGoogle Scholar
  25. 25.
    Vitali G, Parente R, Melotti C. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res 1995; 21: 157–9PubMedGoogle Scholar
  26. 26.
    Frenkel R, McGarry J. Carnitine biosynthesis, metabolism and function [Italian edition]. New York (NY): Academic Press, 1984Google Scholar
  27. 27.
    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: 292–300PubMedCrossRefGoogle Scholar
  28. 28.
    Agarwal A, Said TM. Carnitines and male infertility. Reprod Biomed Online 2004; 8: 376–84PubMedCrossRefGoogle Scholar
  29. 29.
    Lenzi A, Sgro P, Salacone P, et al. A placebo-controlled doubleblind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril 2004; 81: 1578–84PubMedCrossRefGoogle Scholar
  30. 30.
    Lewin LM, Beer R, Lunenfeld B. Epididymis and seminal vesicle as sources of carnitine in human seminal fluid: the clinical significance of the carnitine concentration in human seminal fluid. Fertil Steril 1976; 27: 9–13PubMedGoogle Scholar
  31. 31.
    Wetterauer U, Heite HJ. Carnitine in seminal plasma: its significance in diagnostic andrology. Arch Androl 1980; 4: 137–43PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Michele De Rosa
    • 1
  • Bartolomeo Boggia
    • 1
  • Biagio Amalfi
    • 1
  • Stefano Zarrilli
    • 1
  • Angela Vita
    • 2
  • Annamaria Colao
    • 1
  • Gaetano Lombardi
    • 1
  1. 1.Department of Molecular and Clinical Endocrinology and OncologyUniversity of Naples ‘Federico II’NaplesItaly
  2. 2.Andrology Unit, S. Carlo HospitalPotenzaItaly

Personalised recommendations