隨著年輕人健康意識的提高，在「生孩子」這件事上，越來越多的男性加入了「備孕」大軍，相應的保健產品也賣得越來越好。在這些保健品中，多數為「鋅補充劑」和「葉酸補充劑」，並冠以「提高精子質量」的產品宣傳。

小編在某購物網站上搜索發現，相關保健產品琳琅滿目。為什麼「鋅」和「葉酸」會如此大量地用在男性備孕產品中？是商家噱頭，還是真的有效？

有研究表明，精子對氧化應激特別敏感，氧化應激可導致精子染色質損傷、細胞膜過氧化、運動能力受損和細胞凋亡增加。

鋅作為類固醇受體和參與DNA轉錄的金屬酶的組成部分，在精子形成過程中有著重要作用。鋅在精液中的濃度大約是血液中的30倍，這表明鋅可能通過其抗氧化作用影響精液質量。葉酸能夠為DNA合成和甲基化提供碳元素，其中甲基化在生成精子和清除自由基方面至關重要。此外，葉酸的適度利用和生物有效性還依賴於鋅，二者具有協同作用。

所以，在備孕時供男性使用的膳食補充劑通常都含有葉酸和鋅。

雖然有證據表明，葉酸和鋅的組合可能對男性生育力有幫助，但目前仍缺乏大規模臨床試驗的驗證。對此，近期發表於《JAMA》雜誌題為《Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.》的文章給了我們一個新的答案。

以下為內容是對文獻的簡要介紹，對實驗過程不感興趣的讀者可直接看最後的結論。

Abstract摘要

重要性：

基於以往關於精液質量改善的有限證據，市面上用於提高男性生育力的膳食補充劑通常含有葉酸和鋅。但是目前缺乏大規模試驗來驗證這種方法對改善精液質量和活產的療效。

Importance:

Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.

目的：

研究每日補充葉酸和鋅對精液質量和活產的影響。

Objective:

To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.

設計、布置及參與者：

該葉酸和鋅補充試驗是一項多中心隨機臨床試驗。2013年6月至2017年12月，在美國4家生殖內分泌和不育症治療研究中心招募計劃治療不育症的夫妻（n＝2370；男性≥18歲，女性18-45歲）。2018年8月進行最後一次取精。2019年4月完成活產和妊娠信息的圖表提取。

Design,Setting,and Participants:

The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.

干預措施：

將男方隨機分組按計劃治療不育症（體外受精、研究中心內的其他治療以及門診的其他治療），並每日分別接受5mg葉酸和30mg鋅（n＝1185），或安慰劑（n＝1185）持續6個月。

Interventions:

Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.

主要觀察指標：

共同的主要觀察指標為活產（源自9個月內出現妊娠）和6個月後的精液質量參數（精子濃度、活力、形態、體積、DNA碎片以及總運動精子數）。

Main Outcomes and Measures:

The co–primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.

結果：

參與隨機分組的2370名男性（平均年齡33歲），其中有1773名（75％）完成了最終6個月的研究隨訪。所有夫妻均提供了活產信息，並有1629名男性（69%）在6個月後進行了精液分析。治療組之間的活產率沒有顯著差異（葉酸和鋅組為404例 [34％]，安慰劑組為416例 [35％]；危險差為-0.9％[95％CI，-4.7％至2.8％ ]）。

6個月後大多數精液質量參數（精子濃度、活力、形態、體積以及總運動精子數）在治療組之間沒有顯著差異。DNA碎片在葉酸和鋅組顯著增加（DNA碎片平均百分比在葉酸和鋅組與安慰劑組分別為29.7%和27.2%；平均差為2.4%[95%CI，0.5%-4.4%]）。葉酸和鋅組比安慰劑組更容易出現消化道症狀（腹部不適或疼痛為66例[6%] vs 40例[3%]，噁心為50例[4%] vs 24例[2%]，嘔吐為32例[3%] vs 17例[1%]）。

Result:

Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).

結論與意義：

在尋求治療不育症的夫妻中，男方使用葉酸和鋅補充劑（與安慰劑組相比）並不能顯著改善精液質量和夫妻的活產率。該研究結果不支持男方使用葉酸和鋅補充劑治療不育症。

Conclusions and relevance:

Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

因此，市面上的相關備孕、治療不育的「鋅」、「葉酸」保健品，大多只能起到心理安慰的效果，實際上並沒有多少幫助，你付的錢可能充實了商家的腰包。#清風計劃##把健康帶回家#

參考文獻：

Schisterman EF, Sjaarda LA, Clemons T, et al. Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial. JAMA.2020;323(1):35–48. doi:10.1001/jama.2019.18714

作者：廣州醫科大學附屬第五醫院 徐煜宇