Male infertility is a significant an issue as female infertility however, it is much less highlighted in the public eye. Infertility or sub fertility is a problem for many couples in the UK, affecting 1 in 7 heterosexual couples. Unexplained infertility occurs in 5-10% of couples trying to conceive this is thought to be due to one third female causes one third male causes and one third combined cause.
Male infertility can be defined as the inability to conceive after 12 months of unprotected intercourse (2 x per week) with same female partner in the absence of female causes or sperm abnormalities confirmed by 2 analyses of sperm count, morphology, motility, or other aspects.
Low fertility can be due to many factors and is often considered by health professionals to be idiopathic meaning there is no known cause. Some of the factors that can contribute to poor fertility include obesity, smoking, environmental toxins, inflammation, and nutritional deficiencies. These can all interfere with either hormone signalling, sperm production or normal sperm morphology and motility or a combination of these.
Some of the most important factors when considering male fertility are;
- Sperm count – the amount of sperm
- Sperm motility – ability to move correctly and sufficiently
- Sperm morphology – form, shape and structure of the sperm
Sperm structure and function is directed by hormonal control and availability of essential nutrients for sperm production.1
Nutrients which are important for male fertility include:
Carnitine – plays a vital role in fatty acid metabolism, transporting fatty acids into the mitochondria to be converted into energy and again a deficiency can lead to reduced energy production. Carnitine concentrations have been found to be very high in the epididymis and testes. Studies which have compared fertile and infertile men have found that fertile men have statistically significantly more carnitine in their seminal sample than infertile men. Also, low levels of plasma carnitine are associated with infertility.2,3
Zinc – found in high concentration in the prostate and testes and is involved in virtually all aspects of male reproduction including hormone metabolism spermatogenesis and sperm motility. It also possesses antioxidant capabilities therefore protects against ROS damage, which is essential for protection of sperm mitochondrial function and DNA
- Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis4
- Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa.
- Co-administration of zinc and folic acid (both involved in RNA and DNA synthesis) significantly improved sperm parameters and increased varicocelectomy outcomes5
Selenium – critical antioxidant also required for production of glutathione, essential for testosterone synthesis and normal sperm maturation and motility. Selenium is an essential constituent of seleno-protein found in mitochondrial capsules within the sperm especially located in the mid-piece and tail, therefore plays a role in sperm structure and supports stability and motility of mature sperm.
- A study showed 3-month supplementation with selenium improved sperm motility in comparison to the placebo
- Supplementation of 300mg of selenium along with 600mg of N-Acetyl-Cysteine improved sperm parameters (count, motility and morphology) in men with idiopathic oligoasthenoteratospermia (significant abnormalities in motility and morphology of sperm)
- Supports spermatogenesis by protecting against ROS6
Lycopene – a naturally synthesised carotenoid present in fruits and vegetables. Its powerful ROS quenching abilities make it a major contributor to the human redox defence system . Lycopene is detected at high concentrations in human testes and seminal plasma with levels that tend to be lower in infertile men.7
CoQ10 – concentrated in the head and mid-piece of the sperm, involved in energy production within the mitochondria and is considered the most crucial and powerful antioxidant in sperm structure.
- Promotes motility, fosters sperm survival and provides optimum energy to assist the sperm’s travel to the oocyte
- Administration of CoQ10 may play a positive role in the treatment of asthenozoospermia, possibly related to not only to its function in the mitochondrial respiratory chain but also to its antioxidant properties.8
- CoQ10 in the sperm and seminal fluid helps to maintain optimal sperm motility9
- Decreased levels have been found in seminal plasma in males with idiopathic and varicocele-associated asthenospermia
Folate and B12 – Folate and B12 are responsible for DNA and RNA synthesis and therefore can support spermatogenesis and are concentrated in the sperm head1
- Low folate levels in seminal plasma are associated with increased sperm DNA damage1,18
- MTHFR C677T polymorphism is associated with an increased risk of idiopathic male infertility 10
- B12 deficiency is strongly associated with reduced sperm motility and count
B6 – essential for the production of testosterone as well as adrenal function and energy production, all of which can an influence on sperm production and function, directly or indirectly.1
Vitamin A – Antioxidant required for cellular growth and differentiation, gene expression and epithelial tissue integrity.
- Low Vitamin A concentrations are associated with abnormal semen parameters in infertile men.
- A study showed that in mice, neonatal exposure to a relatively large dose of BPA causes damage to the motility and morphology of sperm, but the BPA effect is, to some extent, inhibited by a supplement of Vitamin A, and enhanced under Vitamin A deficiency conditions.11
Vit C – Major extracellular antioxidant is found in high concentrations in human semen. It has been shown to prevent both sperm agglutination and oxidative damage and supplementation leads to improved motility and viability.1
- Reduction of dietary Vitamin C from 250mg to 5mg per day ascorbic acid concentration in seminal fluid reduced by 50% and damage to sperm DNA increased by 91%.
- After 1 week of 1000mg and 200mg of vitamin C supplementation sperm count increased by 140% and 112% respectively, and placebo saw no change after 60 days several men in both vitamin C group had impregnated their partners compare to none in the placebo group.
Vit E – Major fat-soluble antioxidant therefore prevents oxidation of cell membranes and essential aspect of sperm health.
- Inhibits free radicle damage to unsaturated fatty acids in sperm membranes and phospholipid membranes of mitochondria
- Treatment of asthenospermic (reduce motility of sperm) patients with oral Vitamin E significantly decreased the MDA (marker of oxidative stress) concentration in spermatozoa and improved sperm motility. Eleven out of the 52 treated patients (21%) impregnated their spouses; nine of the spouses successfully ended with normal term deliveries. No pregnancies were reported in the spouses of the placebo-treated patients.12
- Vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility.13
Omega 3 – Major constituent of sperm and responsible for cells membrane fluidity and therefore motility of spermatozoa.
- Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.14
- Docosahexaenoic acid (DHA, C22:6n-3), and palmitic acid (C16:0) are the predominant PUFA and saturated fatty acids, respectively, in human sperm cells. Higher levels of DHA are concentrated on the sperm’s head or tail varying among different species. However, the human sperm head contains a higher concentration of DHA. Dietary fatty acids influence on sperm fatty acid profiles and it seems that sperm fatty acid profiles are most sensitive to dietary omega-3 PUFA.15
- high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology.16
L-Arginine – Amino Acid required for cellular replication. Used to create nitic oxide, which can protect from lipid peroxidation and is essential for spermatogenesis.
- Studies show that arginine can improve sperm count and motility (4g/day for 3 months)17
Antioxidants and mitochondrial function
On average a man can produce 100 million sperm per day. This mean there is a very high rate of cell replication with a high amount of energy requirement, particularly to ensure that healthy sperm are produced. Sperm also have a unique role to play compared to almost any other cell; they must make a long journey against a current to the oocyte in the female fallopian tube, this is a distance of over 1000 times their own length. Once the sperm reaches its destination it then has to penetrate the oocyte for fertilisation to occur. All of these processes from production to fertilisation require a huge amount of energy (as ATP). Mitochondria, the energy production powerhouses in our cells are fundamental to the ability for these processes to occur. It has been shown that mitochondrial function plays a pivotal role in fertility, and it is interesting to note that all of the factors linked to low fertility have the ability to affect mitochondrial function.
Mitochondria are also the main source of reactive oxygen species (ROS) also known as free radicals, ROS in excess can lead to damage and loss of function to any cell including sperm cells. However, in appropriate, controlled levels ROS have been shown to be required for proper sperm function particularly motility and fertilising ability as well as capacitation, the acrosome reaction and hyper-activation (all essential for oocyte penetration). However mitochondrial dysfunction can increase ROS and excess ROS can lead to damage to mitochondria inhibiting their function by causing membrane peroxidation and loss of motility, therefore it is essential that oxidative stress is managed and only occurs at appropriate levels.
Furthermore, studies have found a direct relationship between the activity of sperm mitochondrial enzymes and sperm parameters, including concentration, vitality and motility. Therefore, the higher the activity of the mitochondria, the more energy is produced resulting in improved sperm count and motility.
Sperm mitochondria may also serve as intracellular calcium (Ca²⁺) stores, although their role in signalling is still unclear it is thought that Ca2+ is utilised in the acrosomal head and it may be of importance for oocyte penetration.
Nutrients to support mitochondrial health and therefore fertility include1
Thiamine (B1) – Co factor in the essential step which converts pyruvate into acetyl CoA
Riboflavin (B2) – Also known as FAD, accepts electrons and donated to the electron transport chain (ETC) in order to produce ATP (energy)
Niacin (B3) – Also known as NADH (similar to FAD) accepts and donates electron to ETC in order to produce ATP.
Pantothenic Acid (B5) – carrier of Coenzyme A, essential for Acetyl CoA and therefore energy production
CoQ10 (Ubiquinol) – utilised as a carrier in complex II of ETC. CoQ10 also has antioxidant properties and is found in high concentrations in the head and mid-piece of the sperm. It is considered to promote motility, foster sperm survival and provide optimal energy.
Magnesium – binds to ATP and affects its structure making energy more easily available.
All of the above really help to support mitochondrial function which has been found to be pivotal for healthy sperm production and function and hence male fertility. However, although very important other factors as mentioned above should be investigated when looking at supporting male fertility. The overall health of the individual should be considered and imbalances of any system in the body including the gut, adrenals and thyroid as well as nutritional deficiencies should be addressed.
- Male infertility is a common problem and contributes equally to problems with couples conceiving as female infertility.
- Much of male infertility is considered to be idiopathic (without known cause) but is consistent with many factors including obesity, smoking, environmental toxins, inflammation and nutritional deficiencies. These can all interfere with either hormone signalling, sperm production or normal sperm morphology and motility or a combination of these.
- Some of the most important factors when considering male fertility are perm count, motility and morphology. These are affected by hormonal control and availability of essential nutrients for sperm production.
- Nutrients important for sperm production and therefore male fertility include zinc, selenium, CoQ10, vitamin C, vitamin E, B vitamins (especially folate, B12 and B6), l-carnitine, omega 3 fatty acids and l-arginine
- Sperm have a really high energy requirement and therefore mitochondrial function is essential for normal function. Nutrients that support mitochondrial function such as B vitamins, alpha lipoic acid, magnesium, CoQ10 and l-carnitine support energy production by the mitochondria and therefore can support
- Antioxidants are important for protecting both mitochondrial function and that of cell membranes, which are heavily prone to oxidative stress in sperm.
If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.
Amanda Williams and the Cytoplan Editorial Team
- Textbook of Functional Medicine (2008) Elsevier
- Piomboni P, Focarelli R, Stendardi A, Ferramosca A, Zara V. The role of mitochondria in energy production for human sperm motility. Int J Androl. 2012 Apr;35(2):109-24. doi: 10.1111/j.1365-2605.2011.01218.x. Epub 2011 Sep 27. PMID: 21950496.
- Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta. 2016;1863(10):2422-2435. doi:10.1016/j.bbamcr.2016.01.023
- Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. Experientia. 1994 Jul 15;50(7):626-40. doi: 10.1007/BF01952862. PMID: 8033970.Cassina A, Silveira P, Cantu L, Montes JM, Radi R, Sapiro R. Defective Human Sperm Cells Are Associated with Mitochondrial Dysfunction and Oxidant Production. Biol Reprod. 2015 Nov;93(5):119. doi: 10.1095/biolreprod.115.130989. Epub 2015 Oct 7. PMID: 26447142.
- Azizollahi G, Azizollahi S, Babaei H, Kianinejad M, Baneshi MR, Nematollahi-mahani SN. Effects of supplement therapy on sperm parameters, protamine content and acrosomal integrity of varicocelectomized subjects. J Assist Reprod Genet. 2013 Apr;30(4):593-9.
- Albert Salas-Huetos, Nuria Rosique-Esteban, Nerea Becerra-Tomás, Barbara Vizmanos, Mònica Bulló, Jordi Salas-Salvadó, The Effect of Nutrients and Dietary Supplements on Sperm Quality Parameters: A Systematic Review and Meta-Analysis of Randomized Clinical Trials, Advances in Nutrition, Volume 9, Issue 6, November 2018, Pages 833–848
- Ahmad Majzoub, Ashok Agarwal (2018) Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate, Arab Journal of Urology,Volume 16, Issue 1, Pages 113-124,
- Mancini A, Balercia G. Coenzyme Q(10) in male infertility: physiopathology and therapy. Biofactors. 2011 Sep-Oct;37(5):374-80. doi: 10.1002/biof.164. Epub 2011 Oct 11. PMID: 21989906.
- Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, Ricciardo-Lamonica G, Boscaro M, Lenzi A, Littarru G. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2009 May;91(5):1785-92. doi: 10.1016/j.fertnstert.2008.02.119. Epub 2008 Apr 8. PMID: 18395716.
- Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between Genetic Polymorphisms of Methylenetetra hydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility. Reproductive Sciences. 2011;18(3):304-315.
- Aikawa, H., Koyama, S., Matsuda, M. et al. Relief effect of vitamin A on the decreased motility of sperm and the increased incidence of malformed sperm in mice exposed neonatally to bisphenol A. Cell Tissue Res 315, 119–124 (2004).
- Suleiman, M. Elamin Ali, Zaki, El-malik, Nasr (1996) ‘Lipid Peroxidation and Human Sperm Motility: Protective Role of Vitamin E’, Journal of Andrology
- Amaral A, Lourenço B, Marques M, Ramalho-Santos J. Mitochondria functionality and sperm quality. Reproduction. 2013 Oct 1;146(5):R163-74. doi: 10.1530/REP-13-0178. PMID: 23901129.
- 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
- Esmaeili V, Shahverdi AH, Moghadasian MH, Alizadeh AR. Dietary fatty acids affect semen quality: a review. Andrology. 2015 May;3(3):450-61. doi: 10.1111/andr.12024. Epub 2015 May 7. PMID: 25951427.
- Attaman JA, Toth TL, Furtado J, Campos H, Hauser R, Chavarro JE. Dietary fat and semen quality among men attending a fertility clinic. Hum Reprod. 2012 May;27(5):1466-74.
- Stanislavov R, Rohdewald P. Sperm quality in men is improved by supplementation with a combination of L-arginine, L-citrullin, roburins and Pycnogenol®. Minerva Urol Nefrol. 2014 Dec;66(4):217-23.
- A ZC, Yang Y, Zhang SZ, Li N, Zhang W. Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia. Asian J Androl. 2007 Jan;9(1):57-62.
- Ramalho-Santos J, Varum S, Amaral S, Mota PC, Sousa AP, Amaral A. Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells. Hum Reprod Update. 2009 Sep-Oct;15(5):553-72. doi: 10.1093/humupd/dmp016. Epub 2009 May 4. PMID: 19414527.
- Chen H, Pu XY, Zhang RP, A ZC. Association of common SNP rs1136410 in PARP1 gene with the susceptibility to male infertility with oligospermia. J Assist Reprod Genet. 2014;31(10):1391-1395. doi:10.1007/s10815-014-0311-3
- 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. PMID: 8957697.
- Walczak-Jedrzejowska R, Wolski JK, Slowikowska-Hilczer J. The role of oxidative stress and antioxidants in male fertility. Cent European J Urol. 2013;66(1):60-7. doi: 10.5173/ceju.2013.01.art19. Epub 2013 Apr 26. PMID: 24578993; PMCID: PMC3921845.
- Mora-Esteves C, Shin D. Nutrient supplementation: improving male fertility fourfold. Semin Reprod Med. 2013 Jul;31(4):293-300. doi: 10.1055/s-0033-1345277. Epub 2013 Jun 17. PMID: 23775385.