ABSTRACT
STUDY QUESTION: What is the evidence for over-the-counter antioxidant supplements for male infertility? SUMMARY ANSWER: Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality. WHAT IS KNOWN ALREADY: The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements. STUDY DESIGN SIZE DURATION: Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements. PARTICIPANTS/MATERIALS SETTING METHODS: Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design. MAIN RESULTS AND THE ROLE OF CHANCE: There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial. LIMITATIONS REASONS FOR CAUTION: As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language). WIDER IMPLICATIONS OF THE FINDINGS: This is the first review that gives an insight into the market of male fertility supplements as available to infertility patients and other men seeking to improve their fertility. Earlier reviews have focused only on supplements with published clinical trials. However, we show that more than half of the supplements have not been tested in a clinical trial. To our knowledge, this review is the first to assess the dosage of supplements in relation to the RDA. In agreement with the literature, we found that the evidence on male fertility supplements is generally of poor quality. This review should urge pharmaceutical companies to evaluate their products in randomized controlled trials in order to provide people with substantiated information. STUDY FUNDING/COMPETING INTERESTS: The research position of W.R.d.L. is funded by an unrestricted grant from Goodlife Pharma. W.R.d.L., K.F., and J.P.d.B. are in the research team of a clinical trial on Impryl®, one of the supplements included in this review. REGISTRATION NUMBER: N/A.
ABSTRACT
BACKGROUND: Fecal incontinence is the uncontrollable loss of stool and has a prevalence of around 7-15%. This condition has serious implications for patients' quality of life. Current treatment options show unsatisfactory results. A novel treatment option is therefore needed. OBJECTIVE: This systematic review aims to perform a quality assessment and to give a critical overview of the current research available on regenerative medicine as a treatment for fecal incontinence. STUDY DESIGN: A systematic search strategy was applied in PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, and Cinahl from inception until March of 2018. Studies were found relevant when the animals or patients in the studied group had objectively determined or induced fecal incontinence, and the intervention must have used any kind of cells, stem cells, or biocompatible material, with or without the use of trophic factors. Studies were screened on title and consecutively on abstract for relevance by 2 independent investigators. The risk of bias of preclinical studies was assessed using the SYstematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies, and for clinical studies the Cochrane risk of bias tool for randomized trials was used. RESULTS: In all, 34 preclinical studies and 5 clinical studies were included. Animal species, type of anal sphincter injury, intervention, and outcome parameters were heterogenous. Therefore, a meta-analysis could not be performed. The overall risk of bias of the included studies was high. CONCLUSION: The efficacy of regenerative medicine to treat fecal incontinence could not be determined due to the high risk of bias and heterogenicity of the available preclinical and clinical studies. The findings of this systematic review may result in improved study design of future studies, which could help the translation of regenerative medicine to the clinic as an alternative to current treatments for fecal incontinence.
