Combination of Antioxidants Improves Sperm DNA Fragmentation

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Combination of antioxidants improves sperm DNA fragmentation

The effect of micronutrient supplementation on spermatozoa DNA integrity in subfertile men and subsequent pregnancy rate

doi.org/10.1080/09513590.2021.1923688

Background

Studies show that sperm DNA integrity plays an essential role in fertilisation and early pregnancy with increased DNA fragmentation linked to decreased pregnancy rates and higher rates of miscarriage.

Approximately 8% of men with decreased DNA integrity have normal semen parameters. A DNA fragmentation index (DFI) greater than 15% is commonly associated with male infertility.

Treatment of impaired sperm DNA integrity with standard fertility medications, such as gonadotropins, have shown inconsistent results limiting treatment options to IVF procedures.

However normal spermatogenesis and DNA synthesis requires a variety of vitamins, trace elements and amino acids, with infertile males displaying a need for increased levels of these micronutrients.

A previous study showed improved sperm cell DNA integrity, after subfertile/infertile males took a standard combination of mostly antioxidative micronutrients for 3 months, however this finding was left open to debate because of the indirect testing method for DNA integrity (sperm-hyaluronan binding assay).

Aim

To evaluate the effect of dietary management with a micronutrient formulation on DFI values in subfertile/infertile men, as measured via sperm chromatin dispersion testing, and subsequent pregnancy rates.

Methodology

Males aged 18 to 65 years old with an initial diagnosis of infertility undertook a second sperm analysis and the sperm chromatin dispersion (SCD) test.

Males with abnormal results were then offered the micronutrient supplement + lifestyle changes (healthy diet, exercise, no alcohol, cigarettes, illicit drugs etc.) for a period of 3 months.

Each micronutrient capsule, taken twice daily, contained: L-carnitine (440mg), L-arginine (250mg), zinc (40mg), vitamin E (120mg), glutathione (80mg), selenium (60μg), coenzyme Q10 (15mg) and folic acid (800μg).

Any males diagnosed with azoospermia, aspermia, varicocele and urogenital infections were automatically excluded from the study to minimise potential bias.

The control group consisted of males who opted for lifestyle changes alone. At the end of the study period a second sperm analysis and SCD test was performed.

The impact of both interventions on pregnancy rates was followed for 6 months after the last SCD test.

Results

In total 339 subfertile males satisfied the inclusion exclusion criteria, with 162 males agreeing to take the micronutrient supplement, and 177 opting for lifestyle changes alone.

No significant difference in age (35.7 vs. 35.5 years) or BMI (27.4 vs. 27.0 kg/m2) was observed between the supplement and control groups.

Initial analysis comparing supplement and control groups, for all DFI values, showed significant improvements in DFI after 3 months.

GroupnBefore
DFI (%)
After
DFI (%)
P-value
Supplement16210.56.50.001
Control17710.09.10.06

In the following 6 months, there was 45 and 27 pregnancies, among the supplement and control groups respectively, culminating in a pregnancy rate of 27.8% and 15.3% respectively.

Next analysis, comparing supplement and control groups, in males with DFI > 15%, showed even greater improvements in DFI after 3 months.

GroupnBefore
DFI (%)
After
DFI (%)
P-value
Supplement4620.49.90.001
Control3520.315.00.001

In this sub-group of males, the difference in pregnancy rates was even greater, with 19 and 8 pregnancies, among the supplement and control groups respectively, resulting in a pregnancy rate of 41.3% and 22.9%.

Overall 3 months of lifestyle changes in subfertile/infertile males had positive effects on DFI values and was further improved by the addition of antioxidative micronutrient supplementation.

SUMMARY: ANTIOXIDATIVE SUPPLEMENTS TO IMPROVE SPERM DNA FRAGMENTATION

In this study, combined supplementation of the following antioxidative micronutrients: L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 and folic acid significantly improved sperm DNA fragmentation (6.5% vs. 10.5%) and increased pregnancy rates (27.8% vs. 15.3%).

Limitations

  1. Retrospective study
  2. Non-placebo controlled group

Funding

No external funding was declared for this study.

Glossary

Aspermia
A complete absence of semen during ejaculation.

Azoospermia
A complete absence of sperm in ejaculated semen.

n
Sample size.

P-value
The probability that a result occurred by random chance.

Spermatogenesis
The process by which a complex, interdependent population of germ cells produces spermatozoa (sperm).

Varicocele
An enlargement of veins within the scrotum.

Similar studies

Cheng J B, et al. (2018). L-carnitine combined with coenzyme Q10 for idiopathic oligoasthenozoospermia: A double-blind randomizided controlled trial. https://pubmed.ncbi.nlm.nih.gov/30157357/

Zhao J, et al. (2016). Zinc levels in seminal plasma and their correlation with male infertility: a systematic review and meta-analysis. https://doi.org/10.1038/srep22386

Lipovac M, et al. (2014). Increased hyaluronan acid binding ability of spermatozoa indicating a better maturity, morphology and higher DNA integrity after micronutrient supplementation. https://emj.emg-health.com/

Atig F, et al. (2012). Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. https://doi.org/10.1186/1471-2490-12-6

Swane B G, et al. (2012). Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice. https://doi.org/10.1016/j.mrfmmm.2012.07.002

Keskes-Ammar L, et al. (2003). Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. https://doi.org/10.1080/01485010390129269


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