The role of food supplements in the treatment of the infertile man

      This paper is only available as a PDF. To read, Please Download here.


      Recently, concerns have been raised about the presumptive increased risk of serious undesirable side effects in children born after IVF and intracytoplasmic sperm injection (ICSI). These treatments must, therefore, be reserved as the ultimate option after evidence-based and cause-directed treatment of the male patient with deficient semen has been exhausted. The present authors found that sperm quality and function improved with the intake of complementary food supplementation using a combination of zinc and folic acid, or the antioxidant astaxanthin (Astacarox®), or an energy-providing combination containing (actyl)-carnitine (Proxeed®). Also, double blind trials showed that the latter two substances increase spontaneous or intrauterine insemination- (IUI-) assisted conception rates. Extracts of Pinus maritima bark (Pycnogenol®), which inhibits the cyclo-oxygenase enzyme, reducing prostaglandin production and inflammatory reaction, and extracts of the Peruvian plant Lepidium meyenii were shown to improve sperm morphology and concentration, respectively, in uncontrolled trials. Linseed (flaxseed) oil contains alfa-linolenic acid and lignans. The former corrects the deficient intake of omega-3 essential fatty acids, which is correlated with impaired sperm motility among subfertile men. Lignans are precursors of enterolacton, which inhibits aromatase and reduces the ratio of 16-OH over 2-OH oestrogen metabolites. The resulting reduction in oestrogen load may favourably influence Sertoli cell function.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal


      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Adlercreutz H
        • Bannwart C
        • Wahala K
        • et al.
        Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens.
        Journal of Steroid Biochemistry and Molecular Biology. 1993; 44: 147-153
        • Alvarez JG
        • Storey BR
        Differential incorporation of fatty acids into and peroxidative loss of fatty acids from phospholipids of human spermatozoa.
        Molecular Reproduction and Development. 1995; 42: 334-346
        • Aydin S
        • Inci O
        • Alagol B
        The role of arginine, indomethacin and kallikrein in the treatment of oligoasthenospermia.
        International Urology and Nephrology. 1995; 27: 199-202
        • Bartellini M
        • Canale D
        • Izzo PL
        • et al.
        L-carnitine and acetylcarnitine in human sperm with normal and reduced motility.
        Acta Europaea Fertilitatis. 1987; 18: 29-31
        • Baumann J
        • von Bruchhausen F
        • Wurm G
        Flavonoids and related compounds as inhibition of arachidonic acid peroxidation.
        Prostaglandins. 1980; 20: 627-639
        • Bernard D
        • Christophe A
        • Delanghe J
        • et al.
        The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism.
        Redox Report. 2003; 8: 41-46
        • Bonde JP
        • Joffe M
        • Apostoli P
        • et al.
        Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels.
        Occupational and Environmental Medicine. 2002; 59: 234-242
        • Cho KJ
        • Yun CH
        • Packer L
        • Chung AS
        Inhibition mechanisms of bioflavonoids extracted from the bark of Pinus maritima on the expression of proinflammatory cytokines.
        Annals of the New York Academy of Sciences. 2001; 928: 141-156
        • Christophe A
        • Zalata A
        • Mahmoud A
        • Comhaire F
        Fatty acid composition of sperm phospholipids and its nutritional implications.
        Middle East Fertility Society Journal. 1998; 3: 46-53
        • Comhaire FH
        Treatment of oligospermia with tamoxifen.
        International Journal of Fertility. 1976; 21: 232-238
        • Comhaire FH
        Clinical andrology: from evidence-base to ethics. The ‘E’ quintet in clinical andrology.
        Human Reproduction. 2000; 15: 2067-2071
        • Comhaire FH
        • Vermeulen L
        Effects of high dose oral Kallikrein treatment in men with idiopathic subfertility: evaluation by means of in vitro penetration test of zona free hamster ova.
        International Journal of Andrology. 1983; 6: 168-172
        • Comhaire FH
        • Monteyne R
        • Kunnen M
        The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of “subclinical” varicocele.
        Fertility and Sterility. 1976; 27: 694-698
        • Comhaire FH
        • Rowe PJ
        • Farley TM
        The effect of doxycycline in infertile couples with male accessory gland infection: a double blind prospective study.
        International Journal of Andrology. 1986; 9: 91-98
        • Comhaire FH
        • de Kretser D
        • Farley TM
        • Rowe PJ
        Towards more objectivity in diagnosis and management of male infertility. World Health Organization Task Force on the Diagnosis and Treatment of Infertility.
        International Journal of Andrology. 1987; 7: 1-53
        • Comhaire FH
        • Christophe AB
        • Zalata AA
        • et al.
        The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men.
        Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2000; 63: 159-165
        • 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: 155-159
        • Dawson EB
        • Harris WA
        • Teter MC
        • Powell LC
        Effect of ascobic acid supplementation on sperm quality of smokers.
        Fertility and Sterility. 1992; 58: 1034-1039
        • De Aloysio D
        • Mantuano R
        • Mauloni M
        • Nicoletti G
        The clinical use of arginine aspartate in male infertility.
        Acta Europaea Fertilitatis. 1982; 13: 133-167
        • Depuydt CE
        • Mahmoud AM
        • Dhooge WS
        • et al.
        Hormonal regulation of inhibin B secretion by immature rat sertoli cells in vitro: possible use as a bioassay for estrogen detection.
        Journal of Andrology. 1999; 20: 54-62
        • Eliasson R
        Biochemical analyses of human semen in the study of the physiology and pathophysiology of the male accessory genital glands.
        Fertility and Sterility. 1968; 19: 344-350
        • Fraga CG
        • Motchnik PA
        • Shigenaga MK
        • et al.
        Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.
        Proceedings of the National Academy of Sciences of the USA. 1991; 88: 11003-11006
        • Gerris J
        • Comhaire FH
        • Hellemans P
        • Peeters K
        • Schoonjans F
        Placebo-controlled trial of high-dose Mesterolone treatment of idiopathic male infertility.
        Fertility and Sterility. 1991; 55: 603-607
        • Golan R
        • Weissenberg R
        • Lewin LM
        Carnitine and acetylcarnitine in motile and immotile human spermatozoa.
        International Journal of Andrology. 1984; 7: 484-494
        • Gonzales GF
        • Cordova A
        • Gonzales C
        • et al.
        Lepidium meyenii (Maca) improved semen parameters in adult men.
        Asian Journal of Andrology. 2001; 3: 301-303
        • Gonzales GF
        • Ruiz A
        • Gonzales C
        • et al.
        Effect of Lepidium meyenii (maca) roots on spermatogenesis of male rats.
        Asian Journal of Andrology. 2001; 3: 231-233
        • Goto S
        • Kogure K
        • Abe K
        • et al.
        Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin.
        Biochemical and Biophysical Acta. 2001; 1512: 251-258
        • Hansen M
        • Kurinczuk JJ
        • Bower C
        • Webb S
        The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization.
        New England Journal of Medicine. 2002; 346: 725-730
        • Hargreave TB
        Debate on the pros and cons of varicocele treatment—in favour of varicocele treatment.
        Human Reproduction. 1995; 10: 151-157
        • Hellinga G
        Investigation of the semen.
        in: Clinical Andrology. William Heinmann Medical Books, London1976: 15-29
        • Hughes CM
        • Lewis SE
        • McKelvey-Martin VJ
        • Thompson W
        The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity.
        Human Reproduction. 1998; 13: 1240-1247
        • Irvine DS
        • Twigg JP
        • Gordon EL
        • et al.
        DNA integrity in human spermatozoa: relationships with semen quality.
        Journal of Andrology. 2000; 21: 33-44
        • Iwamoto T
        • Hosoda K
        • Hirano R
        • et al.
        Inhibition of low-density lipoprotein oxidation by astaxanthin.
        Journal of Atherosclerosis and Thrombosis. 2000; 7: 216-222
        • Jeulin C
        • Lewin LM
        Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa.
        Human Reproduction Update. 1996; 2: 87-102
        • Katz P
        • Nachtigall R
        • Showstack J
        The economic impact of the assisted reproductive technologies.
        Nature Cell Biology. 2002; 4: s29-s32
        • Kent-First MG
        • Kol S
        • Muallem A
        • et al.
        The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers.
        Molecular Human Reproduction. 1996; 2: 943-950
        • Kessopoulou E
        • Powers HJ
        • Sharma KK
        • et al.
        A double blind randomized placebo crossover controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility.
        Fertility and Sterility. 1995; 64: 825-831
        • Kohengkul S
        • Tanphaichitr V
        • Muangmun V
        • Tanphaichitr N
        Levels of L-carnitine and L-O-acetylcarnitine in normal and infertile human semen: a lower level of L-O-acetycarnitine in infertile semen.
        Fertility and Sterility. 1977; 28: 1333-1336
        • Koudstaal J
        • Bruinse HW
        • Helmerhorst FM
        • et al.
        Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch University hospitals.
        Human Reproduction. 2000; 15: 935-940
        • Lenzi A
        • Culasso F
        • Gandini L
        • et al.
        Placebo-controlled, double-blind, crossover trial of glutathione therapy in male infertility.
        Human Reproduction. 1993; 8: 1657-1662
        • Lenzi A
        • Lombardo F
        • Sgro P
        • et al.
        Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial.
        Fertility and Sterility. 2003; 79: 292-300
        • Lewin A
        • Lavon H
        The effect of coenzyme Q10 on sperm motility and function.
        Molecular Aspects of Medicine. 1997; 18: 13-19
        • Ma K
        • Sharkey A
        • Kirsch S
        • et al.
        Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome.
        Human Molecular Genetics. 1992; 1: 29-33
        • MacLeod J
        An analysis in human semen of a staining method for differentiating live and dead spermatozoa.
        Anatomical Record. 1942; 83: 573-578
        • Mahmoud AM
        • Comhaire FH
        • Depuydt CE
        The clinical and biologic significance of serum inhibins in subfertile men.
        Reproductive Toxicology. 1998; 12: 591-599
        • Mahmoud A
        • Kiss P
        • Kaufman JM
        • et al.
        The influence of age and lead exposure on inhibin B serum levels in men.
        International Journal of Andrology. 2000; 23 (abstr.): PO94
        • Mayerhofer A
        • Meineke V
        • Köhn FM
        • Frungieri M
        O-03 Cyclooxygenase (COX-2) in male infertility: a new link between prostaglandins and testicular fibrosis?.
        Andrologia. 2002; 34 (abstr.).: 272
        • Meachem SJ
        • Nieschlag E
        • Simoni M
        Inhibin B in male reproduction: pathophysiology and clinical relevance.
        European Journal of Endocrinology. 2001; 145: 561-571
        • Menchini-Fabris GF
        • Canale D
        • Izzo PL
        • et al.
        Free L-carnitine in human semen: its variability in different andrologic pathologies.
        Fertility and Sterility. 1984; 42: 263-267
        • Moll AC
        • Imhof SM
        • Cruysberg JRM
        • et al.
        Incidence of retinoblastoma in children born after in-vitro fertilisation.
        Lancet. 2003; 361: 309-310
        • Moncada ML
        • Vicari E
        • Cimino C
        • et al.
        Effect of acetylcarnitine treatment in oligoasthenospermic patients.
        Acta Europaea Fertilitatis. 1992; 23: 221-224
        • Palermo G
        • Joris H
        • Devroey P
        • Van Steirteghem AC
        Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte.
        Lancet. 1992; 340: 17-18
        • Pryor JP
        • Blandy JP
        • Evans P
        • et al.
        Controlled clinical trial of arginine for infertile men with oligozoospermia.
        British Journal of Urology. 1978; 50: 47-50
        • Rohdewald P
        A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology.
        International Journal of Clinical Pharmacology and Therapeutics. 2002; 40: 158-168
        • Rolf C
        • Cooper TG
        • Yeung CH
        • Nieschlag E
        Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double blind study.
        Human Reproduction. 1999; 14: 1028-1033
        • Roseff SJ
        • Gulati R
        Improvement of sperm quality by Pycnogenol.
        European Bulletin of Drug Research. 1999; 7: 33-36
        • Rowe PJ
        • Comhaire FH
        • Hargreave TB
        • Mahmoud AMA
        WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge University Press, Cambridge2000
        • Ruiz-Pesini E
        • Alvarez E
        • Enriquez JA
        • Lopez-Perez MJ
        Association between seminal plasma carnitine and sperm mitochondrial enzymatic activities.
        International Journal of Andrology. 2001; 24: 335-340
        • Rümke P
        Autospermagglutinins: a cause of infertility in men.
        Annals of the New York Academy of Sciences. 1965; 124: 696-701
        • Schill W-B
        • Krizic A
        • Rjosk H
        Determination of various semen parameters and sex hormone levels in subfertile men during kallikrein therapy.
        Advances in Experimental Medicine and Biology. 1979; 120A: 537-546
        • Scott R
        • Macpherson A
        • Yates RW
        • et al.
        The effect of oral selenium supplementation on human sperm motility.
        British Journal of Urology. 1998; 82: 76-80
        • Sharpe RM
        The ‘oestrogen hypothesis’ – where do we stand now?.
        International Journal of Andrology. 2003; 26: 2-15
        • Soufir JC
        • Ducot B
        • Marson J
        • et al.
        Levels of seminal free L(-) carnitine in fertile and infertile men.
        International Journal of Andrology. 1984; 7: 188-197
        • Stromberg B
        • Dahlquist G
        • Ericson A
        • et al.
        Neurological sequelae in children born after in-vitro fertilisation: a population-based study.
        Lancet. 2002; 359: 461-465
        • Sutcliffe AG
        • Taylor B
        • Li J
        • et al.
        Children born after intracytoplasmic sperm injection: population control study.
        British Medical Journal. 1999; 318: 704-705
        • Tanphaichitr N
        In vitro stimulation of human sperm motility by acetylcarnitine.
        International Journal of Fertility. 1977; 22: 85-91
        • Tiepolo L
        • Zuffardi O
        Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm.
        Human Genetics. 1976; 34: 119-124
        • Tournaye H
        ICSI: a technique too far?.
        International Journal of Andrology. 2003; 26: 63-69
        • van der Ven K
        • Peschka B
        • Montag M
        • et al.
        Increased frequency of congenital chromosomal aberrations in female partners of couples undergoing intracytoplasmic sperm injection.
        Human Reproduction. 1998; 13: 48-54
        • van Dissel-Emiliani FM
        • Grootenhuis AJ
        • De Jong FH
        • de Rooij DG
        Inhibin reduces spermatogonial numbers in testes of adult mice and Chinese hamsters.
        Endocrinology. 1989; 125: 1899-1903
        • Vanhoorne M
        • Comhaire FH
        • De Bacquer D
        Epidemiological study of the effects of carbon disulfide on male sexuality and reproduction.
        Archives of Environmental Health. 1994; 49: 273-278
        • Virgili F
        • Kim D
        • Packer L
        Procyanidins extracted from pine bark protect alpha-tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite.
        FEBS Letters. 1998; 431: 315-318
        • Vitali G
        • Parente R
        • Melotti C
        Carnitine supplementation in human idiopathic asthenospermia: clinical results.
        Drugs under Experimental and Clinical Research. 1995; 21: 157-159
      1. Voliani S, Bertozzi MA, Rossi P, Menchini-Fabris GF 2001 The treatment of male infertility with L-carnitine/L-acetyl carnitine. XVII National Congress, Societa Italiana Andrologia SIA, Venezia 2001 8, 122 (abstr.).

        • Wang C
        • Makela T
        • Hase T
        • et al.
        Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes.
        Journal of Steroid Biochemistry and Molecular Biology. 1994; 50: 205-212
        • Wennerholm U
        • Bergh C
        • Hamberger L
        • et al.
        Incidence of congenital malformations in children born after ICSI.
        Human Reproduction. 2000; 15: 944-948
        • WHO
        WHO laboratory manual of the examination of human semen and semen-cervical mucus interaction. 1st edn. Press Concern, Singapore1980
        • WHO
        WHO laboratory manual of the examination of human semen and sperm-cervical mucus interaction. 2nd edn. Cambridge University Press, Cambridge1987
        • WHO
        A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. World Health Organization.
        International Journal of Andrology. 1992; 15: 299-307
        • WHO
        WHO laboratory manual of the examination of human semen and sperm-cervical mucus interaction. 4th edn. Cambridge University Press, Cambridge1999
        • Wildman REC
        • Medeiros DM
        Advanced human nutrition. CRC Press, London2000: 370-371
        • Wong WY
        • Merkus HM
        • Thomas CM
        • et al.
        Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.
        Fertility and Sterility. 2002; 77: 491-498
        • Zalata AA
        • Christophe AB
        • Depuydt CE
        • et al.
        The fatty acid composition of phospholipids of spermatozoa from infertile patients.
        Molecular Human Reproduction. 1998; 4: 111-118
        • Zheng BL
        • He K
        • Kim CH
        • et al.
        Effect of a lipidic extract from Lepidium meyenii on sexual behavior in mice and rats.
        Urology. 2000; 55: 598-602