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Deep Dive: Investigating the effects of folate and zinc on male fertility

While folate and zinc are essential for processes necessary for male fertility, it may be possible to have too much of a good thing.

Study under review: Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.

Introduction

Infertility, which is defined[1] as the inability to conceive after one year of regular, unprotected sex, affects[2] around 9% of couples of reproductive age, globally. It is estimated[3] that male infertility contributes to approximately half of all infertility cases, and affects about one in 20 adult men younger than 40 years of age.

Although the pathogenesis of male infertility is still poorly understood, several genetic[4], environmental[5], and lifestyle[6] factors like nutrition are implicated. Healthy, balanced diets rich in omega-3 fatty acids, antioxidants, and vitamins are associated[7] with improved semen quality and male fertility.

Two micronutrients that have received a lot of attention in recent years due to their potential for improving male fertility are folate and zinc. Folate is involved in DNA synthesis[8], which is critical for the production of sperm, and folic acid, the synthetic form of folate, is an antioxidant[9], which means that it may minimize the toxic effects of oxidative stress in male sperm cells. Zinc is the second most abundant trace metal in the body after iron, and is found in the testicles and semen in extremely high concentrations[10] relative to other body fluids and tissues. As a cofactor for more than 80 metalloenzymes involved in DNA transcription and protein synthesis, and due to its anti-apoptotic[11] and antioxidant[12] properties, it seems to be essential in the development of the testicles, and in the production and motility of sperm.

Despite the biologically plausible effects of folate and zinc on sperm production and improved semen quality, trials in humans have generally employed small sample sizes and produced conflicting results. Although a recent meta-analysis[13] found that folate and zinc supplementation improved some sperm characteristics in infertile men, there was large heterogeneity between the included trials, and the main outcome of interest to most couples, live birth, was not examined. The study under review was the first large-scale randomized trial to assess the effect of combined folic acid and zinc supplementation on semen quality and live birth in couples seeking infertility treatment.

Male infertility affects about one in 20 adult men under 40, and contributes to approximately half of all infertility cases in couples trying to conceive. While folate and zinc have received a lot of attention in recent years due to their potential for improving male fertility, the evidence is currently limited to small trials with conflicting results. Moreover, the main outcome of interest, live birth, has not been sufficiently examined. The study under review was the first large-scale randomized trial to assess the effect of combined folic acid and zinc supplementation on semen quality and live birth.

What was studied?

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The bigger picture

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Other Articles in Issue #64 (February 2020)