The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST)

To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. A multicenter, double-blind, block randomized, placebo-controlled trial titled “The Folic Acid and Zinc Supplementation Trial (FAZST).” Infertility care centers. Male partners (18 years...

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Published in:	Fertility and sterility 2022-01, Vol.117 (1), p.75-85
Main Authors:	Jenkins, Tim, Aston, Kenneth, Carrell, Douglas, DeVilbiss, Elizabeth, Sjaarda, Lindsey, Perkins, Neil, Mills, James L., Chen, Zhen, Sparks, Amy, Clemons, Traci, Chaney, Kayla, Peterson, C. Matthew, Emery, Benjamin, Hotaling, Jim, Johnstone, Erica, Schisterman, Enrique, Mumford, Sunni L.
Format:	Article
Language:	eng
Subjects:	Adolescent Adult Dietary Supplements DNA methylation DNA Methylation - drug effects Double-Blind Method epigenetics Female folic acid Folic Acid - administration & dosage Humans Infant, Newborn Infertility, Male - diet therapy Infertility, Male - epidemiology Infertility, Male - metabolism Live Birth - epidemiology Male Middle Aged Pregnancy Pregnancy Rate Semen Analysis sperm Spermatozoa - drug effects Spermatozoa - metabolism United States - epidemiology Young Adult zinc Zinc - administration & dosage
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Summary:	To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. A multicenter, double-blind, block randomized, placebo-controlled trial titled “The Folic Acid and Zinc Supplementation Trial (FAZST).” Infertility care centers. Male partners (18 years and older) from heterosexual couples (female partners aged 18–45 years) seeking fertility treatment were recruited. Men were randomized 1:1 to receive folic acid (5 mg) and elemental zinc (30 mg) (n = 713) or a matching placebo (n = 757) daily for 6 months. Sperm DNA methylation was analyzed using the EPIC methylation array (Illumina) at 6 months. Differential sperm DNA methylation was assessed at multiple levels (regional, single cytosine phosphate guanine, etc.). We additionally assessed the impact of supplementation on epigenetic age. No significant differences were identified between the treatment and placebo groups although some trends appeared to be present. To determine if these trends were noteworthy, we implemented various permutations and found that the patterns we identified were no more than would be expected by random chance. The data presented here strongly suggest that this supplementation regimen is not effective at altering sperm DNA methylation. These data comport well with previous findings from the FAZST study that found no impact of supplementation on basic semen analysis parameters or live birth. ClinicalTrials.gov Identifier: NCT01857310. El impacto de la suplementación con zinc y ácido fólico en la metilación del ADN de los espermatozoides: resultados de ensayo clínico aleatorizado de suplementación con ácido fólico y zinc (FAZST). Determinar si la suplementación con ácido fólico (5 mg) y zinc (30 mg) durante 6 meses afecta los patrones de metilación del ADN de los espermatozoides. Un ensayo multicéntrico, doble ciego, aleatorizado en bloques, controlado con placebo titulado "El ensayo de suplemento de ácido fólico y zinc (FAZST)". Centros de tratamiento de la infertilidad. Se reclutaron parejas masculinas (mayores de 18 años) de parejas heterosexuales (parejas femeninas de 18 a 45 años) que buscaban tratamiento de fertilidad. Los hombres fueron aleatorizados 1:1 para recibir ácido fólico (5 mg) y zinc elemental (30 mg) (n = 713) o un placebo equivalente (n = 757) diariamente durante 6 meses. Se analizó la metilación del ADN de los espermatozoides utilizando la matriz de metilación EPIC (Illumina) a los 6 meses. Se evaluó la metilación d
ISSN:	0015-0282 1556-5653