Reversing Male InfertilityDecember 2012
By Silas Hoffman
Forty years ago, couples didn't have to wonder if they were going to be able to conceive a baby. Fertility problems were almost unheard of. Now, the problem is so widespread that if fertility rates continue to drop at the current rate, the world's fertility will fall below the global replacement rate in the next 10 to 40 years.1
Although much of the blame is placed on women, the reality is that more than half of all cases of infertility may be related to male factors.2 A 2012 study revealed that just 1 in 4 men have optimal semen quality.3 By some estimates, sperm counts around the world may have dropped by 50% since the 1930s.4
No one knows for sure what's causing this disturbing decline, but it's clear that some of the factors that plague our modern world in general are at least partly to blame. For example, toxic chemicals that act as endocrine disruptors, such as insecticides, flame retardants, and phthalates from plastics, affect hormones responsible for sperm production, and excessive oxidant stress can damage DNA and impair sperm function.5-9 Obesity is an additional factor.10
Despite the alarming increase in male infertility, the good news is that in many cases it's completely reversible. Numerous studies demonstrate that certain nutrients can directly impact sperm quality—and can ultimately result in improved pregnancy rates.11-14
Declining Sperm Quality
In order to understand what causes male factor infertility, we have to understand the concept of sperm quality. Sperm quality is determined by four factors:
- The total number of sperm cells produced (sperm count),
- Their physical attributes (morphology),
- Their ability to move properly once ejaculated (motility), and
- The integrity of their DNA.
Under ideal circumstances, a healthy young American male can produce 300 to 500 million sperm cells per ejaculation—but typically only one will fertilize an egg.15 In the 1940s, most young men routinely produced an average of 100 million sperm cells per mL of semen—well above the roughly 40 million/mL required to assure normal fertility.16 But recent studies of modern young men show a disturbing trend: Sperm concentrations are declining with many men having less than 40 million/mL, the minimum required for reliable, timely impregnation.16,17
Other aspects of sperm quality are at risk as well. Sperm motility (the ability to move forward to reach the egg), the volume of semen per ejaculate, and the number of normal sperm cells carrying undamaged DNA have diminished over the same time period.18-20 Even the volume of the specific testicular cells that produce testosterone has been in decline.21
To resolve all of these male factors using a medical approach would require multiple medications—many of them unproven and with substantial side effects.22-24 Because of that, women are still the ones who undergo fertility treatments in order to allow men with poor sperm quality to father children—even if they're not the underlying cause of the problem.25,26
However, none of that may be necessary. Many studies have demonstrated that certain nutrients can have a direct impact on sperm quality itself, potentially avoiding the need for expensive drugs or invasive procedures.11-14
Carnitine Boosts Fertility Rates
Sperm cells have to travel farther than any other single human cell—and they need a tremendous amount of energy in order to make the trek. That's what makes carnitine such a vital nutrient for men with poor sperm quality.
Carnitine is a vital transporter molecule whose function is to carry high-energy fat compounds into mitochondria, where they are "burned" to release their energy. This helps give sperm the boost they need if they are going to have a chance at fertilizing an egg. This is important because weakly-swimming sperm (asthenozoospermia) is one of the most important reasons for male factor infertility.27
Supplementation with L-carnitine and/or acetyl-L-carnitine has proven benefits on sperm quality.28-34 Doses of 2,000-3,000 mg/day of L-carnitine, and 500-1,000 mg/day of acetyl-L-carnitine have produced increases of sperm count, motility, straight-swimming ability, as well as total normal sperm forms in clinical studies.30-34 When men were treated with carnitine, their partners experienced pregnancy ranging from 22 to 31%. The pregnancy rates in the control groups (not receiving carnitine) ranged from 1.7 to 3.8%.27,35
|Effects of Antioxidants on Sperm Quality|
|Nutrient||Daily Dose||Improvements in Sperm Quality||Improvement in Pregnancy Rate|
|Vitamin C74-77||1,000 mg||Count, motility, structure||100% (in combination with vitamin E)13|
|Vitamin E12,78-80||300 mg to 1000 mg*||Enhances sperm binding to egg, reduced sperm DNA damage||21%|
|Coenzyme Q10 (CoQ10)81-87||60 mg||Count, motility||16%|
|Selenium11,88-92||200 to 225 mcg||Motility (all measures of sperm quality in combination with NAC )91||10.8%(in combination with vitamin E)88|
|N-acetylcysteine (NAC )91||600 mg||Motility, structure, count, and volume||Not yet studied|
|Zinc93-98||66 mg||Count||Not yet studied|
|*Equivalent to 447-1,490 IU d-alpha-tocopherol (natural form) or 666-2,220 IU dl-alpha-tocopherol (synthetic form).99|
Antioxidants Protect Developing Sperm
Because sperm cells need so much energy, they generate oxidation—which can ultimately damage cell membranes, DNA molecules, and the very mitochondria that power the cell in the first place.
There's a well-known association between oxidant stress, the antioxidant capacities of sperm cells and semen, and final sperm quality.36,37 In general, men with elevated markers of oxidation show impaired sperm count and more abnormally-formed cells.9 Conversely, good cellular antioxidant defenses have higher sperm counts and better motility. In other words, men with better sperm quality have higher overall intakes of antioxidant nutrients than men with poor sperm quality.38 That effect seems to be amplified in older men, many more of whom are choosing to start pregnancies than ever before.
A number of antioxidants have proven abilities to boost sperm quality. These include vitamins C and E, coenzyme Q10 (CoQ10), selenium, n-acetylcysteine (NAC), and zinc.
Let's take a look at zinc and NAC, antioxidants with especially potent abilities to enhance sperm quality.
Zinc deficiency is associated with poor sperm quality resulting from increased oxidant stress in seminal plasma, the liquid portion of semen that is responsible for maintaining sperm cells in a healthy state.39,40 Depletion of zinc also reduces the volume of semen produced.41
Studies in both animal models and humans demonstrate significant improvements in sperm quality following zinc supplementation, especially in cases of known infertility. Supplementation increases sperm counts, mobility, and fertilizing capacity, and decreases levels of DNA damage, structural abnormalities in sperm, and levels of antibodies to sperm that can impair sperm quality.42,43 Studies show an increase of as much as 74% in total normal sperm count in previously sub-fertile men taking 66 mg/day of zinc, particularly when folic acid 5,000 mcg/day is added to the supplementation.44
The benefits of zinc supplementation are especially prominent in smokers, whose total body oxidant levels are vastly higher than those of nonsmokers. In addition, smokers accumulate toxic levels of another metal element, cadmium, which accumulates in testicular tissue and further adds to oxidant stress.45 These effects produce substantial losses of sperm quality and fertility in smokers.45 Studies show that zinc supplementation reduces the impact of cadmium toxicity and boosts sperm quality in smokers.45,46
N-acetylcysteine (NAC) is a modified amino acid with potent direct antioxidant effects; it also boosts natural cellular antioxidant systems such as glutathione. NAC was first used to reverse oxidative toxicity produced by overdoses of acetaminophen (Tylenol® and others), and found later use in reducing the viscosity (thickness) of secretions on cystic fibrosis.
Both of these characteristics of NAC make it appealing as a means of boosting overall sperm and semen quality.
As an antioxidant, NAC has been shown to reduce concentrations of destructive reactive oxygen species in human semen, contributing to improvements in motility.47,48 A dose of 600 mg/day of oral NAC improved volume and motility in men with known male factor infertility.48 And, like zinc, NAC's antioxidant powers make it an effective antidote for toxic chemicals that have negative effects on sperm quality: experiments in mice demonstrate that NAC supplementation can reverse the effects of arsenic, a well-known environmental toxin.49
NAC's ability to reduce viscosity in body secretions provides an additional asset. The same 600 mg/day dose reduces semen viscosity, making it easier for sperm to move forward and reach their goal of fertilizing an egg cell.48
NAC, both alone and in combination with selenium supplements, helps to raise serum testosterone levels as well as improving parameters of sperm quality.50
Lycopene Helps Reverse Male Infertility
Lycopene is a natural, plant-derived carotenoid pigment that provides the red color of tomatoes, watermelon, and other fruits. It has powerful antioxidant characteristics and is involved in a variety of other cellular activities as well.
Low intake of lycopene in the diet is associated with poor semen quality and male factor infertility.38,51 However, supplementing with lycopene has been shown to reverse some or all of that damage.
In one study, men with impaired fertility were given 2 mg of lycopene twice daily. The results were impressive: 66% had improved sperm concentration, 53% had improved motility, and 46% showed improved numbers of normal sperm forms.52 Twenty-three percent of men in this study achieved fatherhood.
Another way lycopene enhances sperm quality is by reducing the impact of advanced glycation endproducts (AGEs), the dangerous sugar/protein structures that form over a lifetime of exposure to blood glucose. In one study, supplementing with 20 mg of lycopene daily resulted in decreased presence of sRAGE, a marker of AGE activity in semen.53
Omega-3 Fatty Acids Improve Sperm Count
In addition to their need to travel long distances, sperm cells must have very specific membrane characteristics in order to be able to bind to the membrane of an egg and produce a living embryo. Much of those special characteristics come from the sperm's high levels of omega-3 fatty acids.54,55
Men with defects in sperm quality or sperm counts typically have low levels of omega-3s, or low ratios of omega-3 to omega-6 fats, in their semen and sperm cell composition.54,56,57 On the other hand, higher omega-3 levels and ratios are directly correlated with improved sperm motility, concentration, and structure.54
Lab and animal studies reveal that sperm cells supplemented with omega-3s have improved motility and fewer markers of oxidative stress compared with control cells.58,59 Omega-3 fats, (specifically EPA and DHA), have been found to restore fertility and impaired sperm production in animal studies.60,61 Human studies show that supplementing with 1,840 mg a day of a combination of DHA and EPA improved total sperm count and concentration.62 An omega-3-rich Mediterranean-style diet boosts the chances of successful pregnancy in previously-infertile couples by 40%.61
Vitamin D Deficiency Contributes to Infertility
One study examining spermatozoa quality found 44% of the men studied had 25-hydroxyvitamin D blood levels below 20 ng/mL. Optimal levels are over 50 ng/mL, so these men were seriously deficient in vitamin D, as most people are who don't supplement with more than 5,000 IU/day. This could have a huge impact on the rising rate of male factor infertility. Serum vitamin D levels are positively correlated with sperm motility and normal structure.63
It was not until 2006 that a receptor molecule for vitamin D was detected on the surface of sperm cells.64,65 Since that time, the receptor has been found in all tissues of the male reproductive tract.66
Vitamin D deficiency reduces the ability of male lab animals to deposit sperm in female reproductive tracts by 45%, and the rate of successful pregnancies in females who received sperm from D-deficient males is decreased by 73%.67
However, when vitamin D is added to live human sperm cells in the lab, it produces a sharp increase in sperm motility, along with rapid development of the "acrosome reaction" that allows the sperm cell to attach to the egg.66
Although no human studies have been reported on the impact of vitamin D supplementation on male factor infertility, men facing fertility problems should still consider supplementing with this nutrient—especially given the powerful effects of vitamin D in lab and animal studies, coupled with the high rates of vitamin D insufficiency and deficiency among Americans. At the very least, consider supplementing to bring plasma vitamin D levels into the range considered sufficient by conventional medicine (greater than 32 ng/mL) range. This can often be accomplished by daily supplementation with vitamin D3 at 1,000 to 2,000 IU/day, though up to 5,000 IU is safe and may be needed in certain cases.68-70
Ashwagandha Improves Sperm Quality
Stress is a major factor in the modern infertility epidemic. It increases oxidative damage, inflammation, and other harmful conditions that are known to reduce sperm quality.71
One way to combat stress-related infertility is with a plant used in Ayurvedic and other traditional medical systems for reducing stress. Studies have shown that Ashwagandha (Withania somnifera) can treat stress-related infertility.71
When 60 infertile men took Ashwagandha root powder daily for 3 months, they experienced decreased measures of stress, increased levels of antioxidants, and improved overall sperm quality.71 By the end of the 3 months, the partners of 14% of those men had conceived pregnancies.
Ashwagandha extract works in several ways to improve sperm quality: It inhibits lipid peroxidation, reduces markers of glycation, improves seminal levels of antioxidant enzymes and vitamins A, C, and E, and increases serum testosterone and other reproductively critical hormones.72,73
The global decline in sperm quality, especially prominent in industrialized nations, has the potential to threaten the survival of humankind. Many reasons for this decline have been proposed, the strongest of which have to do with environmental and dietary factors unique to the modern age.
Since male factor infertility accounts for more than half of all infertility cases, it is incumbent upon men to optimize their sperm quality. Sadly, no medication or conventional medical treatment seems capable of reversing this dangerous trend.
Nutritional supplements often hold out hope where pharmaceutical medicine fails, and the area of sperm quality is no exception. Antioxidant and cell energizing nutrients can improve sperm motility, sperm count, and the number of normal sperm cells, while reducing damage to sperm DNA—ultimately improving the chances of successful pregnancy.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialists at 1-866-864-3027.
1. Available at: http://www.economist.com/node/14744915. Accessed September 14, 2012.
2. Visser L, Repping S. Unravelling the genetics of spermatogenic failure. Reproduction. 2010 Feb;139(2):303-7.
3. Jorgensen N, Joensen UN, Jensen TK, et al. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open. 2012;2(4).
4. Merzenich H, Zeeb H, Blettner M. Decreasing sperm quality: a global problem? BMC Public Health. 2010;10:24.
5. Desai N, Sabanegh E, Jr., Kim T, Agarwal A. Free radical theory of aging: implications in male infertility. Urology. 2010 Jan;75(1):14-9.
6. Meeker JD, Stapleton HM. House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parameters. Environ Health Perspect. 2010 Mar;118(3):318-23.7.Meeker JD, Barr DB, Hauser R. Human semen quality and sperm DNA damage in relation to urinary metabolites of pyrethroid insecticides. Hum Reprod. 2008 Aug;23(8):1932-40.
8. Jurewicz J, Hanke W. Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies. Int J Occup Med Environ Health. 2011 Jun;24(2):115-41. Epub 2011 May 19.
9. Shiva M, Gautam AK, Verma Y, Shivgotra V, Doshi H, Kumar S. Association between sperm quality, oxidative stress, and seminal antioxidant activity. Clin Biochem. 2011 Mar;44(4):319-24.
10. Mah PM, Wittert GA. Obesity and testicular function. Mol Cell Endocrinol. 2010 Mar 25;316(2):180-6.
11. Ibrahim HA, Zhu Y, Wu C, et al. Selenium-enriched probiotics improves murine male fertility compromised by high fat diet. Biol Trace Elem Res. 2012 Jun;147(1-3):251-60.
12. Greco E, Romano S, Iacobelli M, et al. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod. 2005 Sep;20(9):2590-4.
13. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Role of male factor in early recurrent embryo loss: do antioxidants have any effect? Fertil Steril. 2009 Aug;92(2):565-71.
14. Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet. 2009 Aug;26(8):427-32.
15. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003627.htm. Accessed September 21, 2012.
16. Andersson AM, Jorgensen N, Main KM, et al. Adverse trends in male reproductive health: we may have reached a crucial 'tipping point'. Int J Androl. 2008 Apr;31(2):74-80.
17. Nordkap L, Joensen UN, Blomberg Jensen M, Jørgensen N. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environmental exposures. Mol Cell Endocrinol. 2012 May 22;355(2):221-30. Epub 2011 Nov 25.
18. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609-13.
19. Feki NC, Abid N, Rebai A, et al. Semen quality decline among men in infertile relationships: experience over 12 years in the South of Tunisia. J Androl. 2009 Sep-Oct;30(5):541-7.
20. Mukhopadhyay D, Varghese AC, Pal M, et al. Semen quality and age-specific changes: a study between two decades on 3,729 male partners of couples with normal sperm count and attending an andrology laboratory for infertility-related problems in an Indian city. Fertil Steril. 2010 May 1;93(7):2247-54.
21. Johnson L, Falk GU, Suggs LC, et al. Heterotopic transplantation as a model to study the regulation of spermatogenesis; some histomorphological considerations about sperm decline in man. Contracept Fertil Sex. 1997 Jul-Aug;25(7-8):549-55.
22. Liu PY, Handelsman DJ. The present and future state of hormonal treatment for male infertility. Hum Reprod Update. 2003 Jan-Feb;9(1):9-23.
23. Isidori AM, Pozza C, Gianfrilli D, Isidori A. Medical treatment to improve sperm quality. Reprod Biomed Online. 2006 Jun;12(6):704-14.
24. Kumar R, Gautam G, Gupta NP. Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol. 2006 Oct;176(4 Pt 1):1307-12.
25. Siddiq FM, Sigman M. A new look at the medical management of infertility. Urol Clin North Am. 2002 Nov;29(4):949-63.
26. Neri QV, Takeuchi T, Rosenwaks Z, Palermo GD. Treatment options for impaired spermatogenesis: germ cell transplantation and stem-cell based therapy. Minerva Ginecol. 2009 Aug;61(4):253-9.
27. Wang YX, Yang SW, Qu CB, et al. L-carnitine: safe and effective for asthenozoospermia. Zhonghua Nan Ke Xue. 2010 May;16(5):420-2.
28. Morgante G, Scolaro V, Tosti C, Di Sabatino A, Piomboni P, De Leo V. Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia. Minerva Urol Nefrol. 2010 Sep;62(3):213-8.
29. Cheng HJ, Chen T. Clinical efficacy of combined L-carnitine and acetyl-L-carnitine on idiopathic asthenospermia. Zhonghua Nan Ke Xue. 2008 Feb;14(2):149-51.
30. Khademi A, Alleyassin A, Safdarian L, Hamed EA, Rabiee E, Haghaninezhad H. The effects of L-carnitine on sperm parameters in smoker and non-smoker patients with idiopathic sperm abnormalities. J Assist Reprod Genet. 2005 Dec;22(11-12):395-9.
31. De Rosa M, Boggia B, Amalfi B, et al. Correlation between seminal carnitine and functional spermatozoal characteristics in men with semen dysfunction of various origins. Drugs R D. 2005;6(1):1-9.
32. 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 Feb;79(2):292-300.
33. Vitali G, Parente R, Melotti C. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res. 1995;21(4):157-9.
34. Costa M, Canale D, Filicori M, D'Lddio S, Lenzi A. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia. 1994 May-Jun;26(3):155-9.
35. Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl. 2004 Sep-Oct;25(5):761-70; discussion 71-2.
36. Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab. 2005 Oct;6(5):495-501.
37. Agarwal A, Sekhon LH. The role of antioxidant therapy in the treatment of male infertility. Hum Fertil (Camb). 2010 Dec;13(4):217-25.
38. Mendiola J, Torres-Cantero AM, Vioque J, et al. A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics. Fertil Steril. 2010 Mar 1;93(4):1128-33.
39. Huang YL, Tseng WC, Cheng SY, Lin TH. Trace elements and lipid peroxidation in human seminal plasma. Biol Trace Elem Res. 2000 Sep;76(3):207-15.
40. Yuyan L, Junqing W, Wei Y, Weijin Z, Ersheng G. Are serum zinc and copper levels related to semen quality? Fertil Steril. 2008 Apr;89(4):1008-11.
41. Hunt CD, Johnson PE, Herbel J, Mullen LK. Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men. Am J Clin Nutr. 1992 Jul;56(1):148-57.
42. Omu AE, Dashti H, Al-Othman S. Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol. 1998 Aug;79(2):179-84.
43. Omu AE, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA, Mathew TC. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract. 2008;17(2):108-16.
44. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8.
45. Al-Bader A, Omu AE, Dashti H. Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc. Arch Androl. 1999 Sep-Oct;43(2):135-40.
46. Garcia PC, Piffer RC, Gerardin DC, Sankako MK, Alves de Lima RO, Pereira OC. Could zinc prevent reproductive alterations caused by cigarette smoke in male rats? Reprod Fertil Dev. 2012;24(4):559-67.
47. Oeda T, Henkel R, Ohmori H, Schill WB. Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility? Andrologia. 1997 May-Jun;29(3):125-31.
48. Ciftci H, Verit A, Savas M, Yeni E, Erel O. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology. 2009 Jul;74(1):73-6.
49. Reddy PS, Rani GP, Sainath SB, Meena R, Supriya C. Protective effects of N-acetylcysteine against arsenic-induced oxidative stress and reprotoxicity in male mice. J Trace Elem Med Biol. 2011 Dec;25(4):247-53.
50. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009 Feb;181(2):741-51.
51. Goyal A, Chopra M, Lwaleed BA, Birch B, Cooper AJ. The effects of dietary lycopene supplementation on human seminal plasma. BJU Int. 2007 Jun;99(6):1456-60.
52. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility--a preliminary report. Int Urol Nephrol. 2002;34(3):369-72.
53. Oborna I, Malickova K, Fingerova H, et al. A randomized controlled trial of lycopene treatment on soluble receptor for advanced glycation end products in seminal and blood plasma of normospermic men. Am J Reprod Immunol. 2011 Sep;66(3):179-84.
54. Aksoy Y, Aksoy H, Altinkaynak K, Aydin HR, Ozkan A. Sperm fatty acid composition in subfertile men. Prostaglandins Leukot Essent Fatty Acids. 2006 Aug;75(2):75-9.
55. Wathes DC, Abayasekara DR, Aitken RJ. Polyunsaturated fatty acids in male and female reproduction. Biol Reprod. 2007 Aug;77(2):190-201.
56. Oborna I, Wojewodka G, De Sanctis JB, et al. Increased lipid peroxidation and abnormal fatty acid profiles in seminal and blood plasma of normozoospermic males from infertile couples. Hum Reprod. 2010 Feb;25(2):308-16.
57. Safarinejad MR, Hosseini SY, Dadkhah F, Asgari MA. Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: a comparison between fertile and infertile men. Clin Nutr. 2010 Feb;29(1):100-5.
58. Brinsko SP, Varner DD, Love CC, Blanchard TL, Day BC, Wilson ME. Effect of feeding a DHA-enriched nutriceutical on the quality of fresh, cooled and frozen stallion semen. Theriogenology. 2005 Mar 15;63(5):1519-27.
59. Gholami H, Chamani M, Towhidi A, Fazeli MH. Effect of feeding a docosahexaenoic acid-enriched nutriceutical on the quality of fresh and frozen-thawed semen in Holstein bulls. Theriogenology. 2010 Dec;74(9):1548-58.
60. Roqueta-Rivera M, Stroud CK, Haschek WM, et al. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice. J Lipid Res. 2010 Feb;51(2):360-7.
61. Vujkovic M, de Vries JH, Lindemans J, et al. The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertil Steril. 2010 Nov;94(6):2096-101.
62. Safarinejad MR. Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study. Andrologia. 2011 Feb;43(1):38-47.
63. Blomberg Jensen M, Bjerrum PJ, Jessen TE, et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod. 2011 Jun;26(6):1307-17.
64. Corbett ST, Hill O, Nangia AK. Vitamin D receptor found in human sperm. Urology. 2006 Dec;68(6):1345-9.
65. Blomberg Jensen M. Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction. 2012 Aug;144(2):135-52.
66. Blomberg Jensen M, Dissing S. Non-genomic effects of vitamin D in human spermatozoa. Steroids. 2012 Aug;77(10):903-9.
67. Kwiecinski GG, Petrie GI, DeLuca HF. Vitamin D is necessary for reproductive functions of the male rat. J Nutr. 1989 May;119(5):741-4.
68. Holick MF. Vitamin D: a D-Lightful health perspective. Nutr Rev. 2008 Oct;66(10 Suppl 2):S182-94.
69. Wimalawansa SJ. Vitamin D: an essential component for skeletal health. Ann N Y Acad Sci. 2011 Dec;1240:E1-12.
70. Wimalawansa SJ. Vitamin D in the new millennium. Curr Osteoporos Rep. 2012 Mar;10(1):4-15.
71. Mahdi AA, Shukla KK, Ahmad MK, et al. Withania somnifera Improves Semen Quality in Stress-Related Male Fertility. Evid Based Complement Alternat Med. 2009 Sep 29.
72. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010 Aug;94(3):989-96.
73. Shukla KK, Mahdi AA, Mishra V, et al. Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations. Reprod Biomed Online. 2011 Mar 7.
74. Thiele JJ, Friesleben HJ, Fuchs J, Ochsendorf FR. Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washed semen. Hum Reprod. 1995 Jan;10(1):110-5.
75. Colagar AH, Marzony ET. Ascorbic Acid in human seminal plasma: determination and its relationship to sperm quality. J Clin Biochem Nutr. 2009 Sep;45(2):144-9.
76. Dawson EB, Harris WA, Teter MC, Powell LC. Effect of ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril. 1992 Nov;58(5):1034-9.
77. Vani K, Kurakula M, Syed R, Alharbi K. Clinical Relevance of Vitamin C Among Lead-Exposed Infertile Men. Genet Test Mol Biomarkers. 2012 Jun 25.
78. Kessopoulou E, Powers HJ, Sharma KK, et al. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril. 1995 Oct;64(4):825-31.
79. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005 May-Jun;26(3):349-53.
80. Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr MA. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl. 1996 Sep-Oct;17(5):530-7.
81. Lewin A, Lavon H. The effect of coenzyme Q10 on sperm motility and function. Mol Aspects Med. 1997;18 Suppl:S213-9.
82. Balercia G, Mancini A, Paggi F, et al. Coenzyme Q10 and male infertility. J Endocrinol Invest. 2009 Jul;32(7):626-32.
83. Balercia G, Mosca F, Mantero F, et al. Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Fertil Steril. 2004 Jan;81(1):93-8.
84. Balercia G, Buldreghini E, Vignini A, et al. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2009 May;91(5):1785-92.
85. Mancini A, De Marinis L, Littarru GP, Balercia G. An update of Coenzyme Q10 implications in male infertility: biochemical and therapeutic aspects. Biofactors. 2005;25(1-4):165-74.
86. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009 Jul;182(1):237-48.
87. Mancini A, Balercia G. Coenzyme Q(10) in male infertility: physiopathology and therapy. Biofactors. 2011 Sep;37(5):374-80.
88. Moslemi MK, Tavanbakhsh S. Selenium-vitamin E supplementation in infertile men: effects on semen parameters and pregnancy rate. Int J Gen Med. 2011;4:99-104.
89. Keskes-Ammar L, Feki-Chakroun N, Rebai T, et al. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl. 2003 Mar-Apr;49(2):83-94.
90. Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol. 1998 Jul;82(1):76-80.
91. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009 Feb;181(2):741-51.
92. Oda SS, El-Maddawy ZK. Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats. Exp Toxicol Pathol. 2011 Apr 6.
93. Kumari D, Nair N, Bedwal RS. Testicular apoptosis after dietary zinc deficiency: ultrastructural and TUNEL studies. Syst Biol Reprod Med. 2011 Oct;57(5):233-43.
94. Akinloye O, Abbiyesuku FM, Oguntibeju OO, Arowojolu AO, Truter EJ. The impact of blood and seminal plasma zinc and copper concentrations on spermogram and hormonal changes in infertile Nigerian men. Reprod Biol. 2011 Jul;11(2):83-98.
95. Yuyan L, Junqing W, Wei Y, Weijin Z, Ersheng G. Are serum zinc and copper levels related to semen quality? Fertil Steril. 2008 Apr;89(4):1008-11.
96. Ebisch IM, Pierik FH, FH DEJ, Thomas CM, Steegers-Theunissen RP. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl. 2006 Apr;29(2):339-45.
97. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8.
98. Omu AE, Dashti H, Al-Othman S. Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol. 1998 Aug;79(2):179-84.
99. Available at: http://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. Accessed September 26, 2012.
100. Stewart AF, Kim ED. Fertility concerns for the aging male. Urology. 2011 Sep;78(3):496-9.
101. Schmid TE, Eskenazi B, Marchetti F, et al. Micronutrients intake is associated with improved sperm DNA quality in older men. Fertil Steril. 2012 Aug 23.
102. Abad C, Amengual MJ, Gosalvez J, et al. Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA. Andrologia. 2012 Sep 3.