Evidence map›Paper›PMID 34656303›Full record

Trial reportFertility and sterility2022

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

Tim Jenkins, Kenneth Aston, Douglas Carrell, Elizabeth DeVilbiss, Lindsey Sjaarda, Neil Perkins, James L Mills, Zhen Chen, Amy Sparks, Traci Clemons and 7 more

Registry-linked trialOpen access · greenAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Fertility and sterility, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01857310 (Folic Acid and Zinc Supplementation Trial), which is not on this map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01857310 nacompletednot on this map

Folic Acid and Zinc Supplementation Trial: A Multi-center, Double-blind, Block-randomized, Placebo-controlled Trial

TypeinterventionalSponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Ran2013 to 2019Enrolled2,370ConditionsPregnancy, Live Birth, Spontaneous AbortionArms5 mg folic acid and 30 mg elemental zinc, Placebo Comparator: Placebo
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Article
  6. Silicon-Based Agent Attenuates Age-Related Spermatogenesis Disorder.International journal of urology : official journal of the Japanese Urological Association · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Micronutrient Antioxidants for Men (MenevitAntioxidants (Basel, Switzerland) · 2024
    Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 1 country.

Tim JenkinsDivision of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah; Department of Cell Biology and Physiology, Brigham Young University, Provo, Utah; Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah.
Kenneth AstonDivision of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah; Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah.
Douglas CarrellDivision of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah; Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
Elizabeth DeVilbissEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Lindsey SjaardaEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Neil PerkinsBiostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
James L MillsEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Zhen ChenBiostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Amy SparksIVF and Andrology Laboratories, Center for Advanced Reproductive Care, Iowa City, Iowa.
Traci ClemonsThe Emmes Company, LLC, Rockville, Maryland.
Kayla ChaneyThe Emmes Company, LLC, Rockville, Maryland.
C Matthew PetersonDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
Benjamin EmeryAndrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah.
Jim HotalingDivision of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
Erica JohnstoneDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
Enrique SchistermanDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Sunni L MumfordEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland. Electronic address: mumfords@mail.nih.gov.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USUniversity of Utah · USEmmes (United States) · USAdvanced Breast Care · USBrigham Young University · USUniversity of Pennsylvania · US

Funding

General collaborationsZIAHD009014 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI CHEN, ZHEN · 2022 to 2025
$312k
Intramural NIH HHS ZIA HD009014NICHD NIH HHS HHSN275201200007CNICHD NIH HHS HHSN275201300026I
6 · The paper itself

Abstract

objectiveTo determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns.

designA multicenter, double-blind, block randomized, placebo-controlled trial titled "The Folic Acid and Zinc Supplementation Trial (FAZST)."

settingInfertility care centers. PATIENT(S): Male partners (18 years and older) from heterosexual couples (female partners aged 18-45 years) seeking fertility treatment were recruited. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): 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. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01857310.

Indexed as

AdolescentAdultDietary SupplementsDNA MethylationDouble-Blind MethodFemaleFolic AcidHumansInfant, NewbornInfertility, MaleLive BirthMaleMiddle AgedPregnancyPregnancy RateSemen AnalysisFolic AcidZincDNA methylationepigeneticsfolic acidspermzinc

Identifiers

PMID34656303
PMCPMC12462768
OpenAlexW3206503865

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.