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Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.
Kubiak, K, Szmidt, MK, Kaluza, J, Zylka, A, Sicinska, E
Antioxidants (Basel, Switzerland). 2023;12(10)
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A deficiency of the thyroid hormone causes hypothyroidism (HT), whereas Autoimmune thyroiditis (AIT) is mainly an organ-specific autoimmune condition. Both HT and AIT are characterised by low-grade inflammation and inflammation in the thyroid gland. Dietary supplements may offer health benefits; however, previous research findings are inconclusive. This systematic review evaluated twenty-two controlled studies to understand the effectiveness of dietary supplements in reducing inflammation and oxidative stress and improving antioxidant and thyroid parameters in patients with HT or AIT. The efficacy of dietary supplements in improving thyroid health and reducing inflammation and oxidative stress was inconclusive due to the low quality of the included studies and the limited number of available studies. Selenium supplements might be beneficial in improving thyroid parameters and inflammation in patients with HT or AIT. Even though the therapeutic benefits of dietary supplements in treating thyroid disease were inconclusive, healthcare professionals can use them to address the common nutritional deficiencies in people with HT and AIT. Further, large, long-term, robust studies are required to assess the therapeutic utility of different dietary supplements in promoting the health of the thyroid gland.
Abstract
This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.
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Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.
Zheng, SH, Chen, XX, Chen, Y, Wu, ZC, Chen, XQ, Li, XL
Reproductive biology and endocrinology : RB&E. 2023;21(1):79
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Endometriosis is a common gynaecological disorder in reproductive-age women which leads to infertility and pain symptoms. Current pain management approaches involve medications and surgical treatments, but their side effects and risk of recurrence have led to the exploration of alternative options. The aim of this study was to clarify the potential effects of antioxidant vitamins supplementation on endometriosis. This study was a systematic review and meta-analysis of eleven studies, comprising a total of 589 patients. Results showed that antioxidant vitamins supplementation can effectively alleviate endometriosis-related pain and reduce inflammatory markers. Authors conclude that antioxidant vitamins supplementation can be considered as an alternative treatment either on its own or in combination with other methods for managing endometriosis-related pain. However, further research would help to provide a clearer understanding of the role of antioxidant vitamins supplementation in women with endometriosis.
Abstract
OBJECTIVE This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION PROSPERO registration number: CRD42023415198.
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Polyphenol Intake in Pregnant Women on Gestational Diabetes Risk and Neurodevelopmental Disorders in Offspring: A Systematic Review.
Salinas-Roca, B, Rubió-Piqué, L, Montull-López, A
Nutrients. 2022;14(18)
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In Europe, gestational diabetes affects approximately 10.9% of pregnant women. According to previous research, the cardiometabolic health of the mother and the mother's dietary habits during pregnancy may affect the foetus' neurodevelopment. Taking polyphenol supplements and eating foods rich in polyphenols is beneficial for promoting health across generations. In this systematic review, fourteen studies were included in order to evaluate the effects of polyphenols on gestational diabetes and mental health in the offspring. A higher prevalence of neurodevelopmental diseases in offspring is associated with gestational diabetes. The results of this systematic review revealed that polyphenol intake during pregnancy might have a beneficial effect on improving cardiometabolic health, reducing inflammation, DNA methylation and oxidative stress, thus reducing the risk of developing fetal neurodevelopmental disorders, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorders. There is a need for further robust research, as the existing evidence regarding the safety of long-term polyphenol supplementation and its effects on gestational diabetes and fetal neurodevelopment is very limited. In spite of this, healthcare professionals can use the findings of this systematic review to learn more about the positive health benefits of polyphenols in pregnant women.
Abstract
The intake of foods containing polyphenols can have a protective role to avoid comorbidities during pregnancy and, at the same time, promote transgenerational health. This review aims to describe the effect of polyphenol intake through supplements or polyphenol-rich foods during pregnancy on the incidence and evolution of gestational diabetes mellitus (GDM), as well as the link with the neurodevelopment of the fetus. Using PRISMA procedures, a systematic review was conducted by searching in biomedical databases (PubMed, Cinahl and Scopus) from January to June 2022. Full articles were screened (n = 419) and critically appraised. Fourteen studies were selected and were divided into two different thematic blocks considering (i) the effect of polyphenols in GDM and (ii) the effect of GDM to mental disorders in the offspring. A positive relationship was observed between the intake of polyphenols and the prevention and control of cardiometabolic complications during pregnancy, such as GDM, which could be related to thwarted inflammatory and oxidative processes, as well as neuronal factors. GDM is related to a greater risk of suffering from diseases related to neurodevelopment, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorder. Further clinical research on the molecule protective mechanism of polyphenols on pregnant women is required to understand the transgenerational impact on fetal neurodevelopment.
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Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.
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Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Yang, K, Chen, J, Zhang, T, Yuan, X, Ge, A, Wang, S, Xu, H, Zeng, L, Ge, J
Frontiers in immunology. 2022;13:949746
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat accumulation in the liver that can result in liver damage. NAFLD affects approximately 25% of the global population. There is evidence that dietary polyphenols can improve metabolism and insulin resistance and reduce inflammation and oxidative stress, which are the mechanisms that lead to liver damage in NAFLD. This systematic review and meta-analysis aimed to assess the effectiveness of dietary polyphenols in the treatment of non-alcoholic fatty liver disease (NAFLD). Eight dietary polyphenols, such as curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein, were evaluated for their efficacy and safety. The administration of 80-3,000 mg of Curcumin for an 8-12 week duration is effective and safe for reducing body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and insulin resistance (HOMA-IR). Compared with the placebo, Naringenin reduced the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Hesperidin may potentially decrease body mass index (BMI), AST, ALT, TG, TC, and HOMA-IR. Catechin is safe, and 500-1000 mg supplementation for 12 weeks may reduce BMI, HOMA-IR, and TG. NAFLD patients who received silymarin showed improvements in ALT and AST, as well as reductions in hepatic fat accumulation and liver stiffness. 94–2100 mg of Silymarin supplementation for 8–48 weeks may reduce liver enzyme levels. Researchers can use the results of this study to understand the clinical utility of different polyphenol supplements in the treatment of NAFLD. Because the current evidence is highly heterogeneous in nature and limited in scope, further robust research is required on various classes of polyphenols and their effectiveness in reducing the severity of NAFLD.
Abstract
Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.
Babcock, MC, DuBose, LE, Witten, TL, Stauffer, BL, Hildreth, KL, Schwartz, RS, Kohrt, WM, Moreau, KL
The Journal of clinical endocrinology and metabolism. 2022;107(2):e500-e514
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Serum testosterone declines gradually with age at a rate of ~1% per year after the third decade. Vascular aging, featuring endothelial dysfunction mediated by oxidative stress and inflammation, is a major risk factor for the development of age-associated cardiovascular disease (CVD). The aim of this study was to examine the effects of low testosterone on cardiovascular aging in men. This study is a cross-sectional study which recruited 58 healthy men of all races/ethnic backgrounds aged 50-75 years (middle-aged/older) and 18-40 years (young). Results show that middle-aged/older men with lower testosterone have evidence of “accelerated” vascular aging, as indicated by a greater age-associated endothelial dysfunction of large arteries compared with their age-matched peers. The greater macrovascular endothelial dysfunction in middle-aged/older men with chronically low testosterone was independent of CVD risk factors or symptoms of androgen deficiency. Furthermore, increased systemic oxidative stress and inflammation are mechanistically linked to the greater age-associated endothelial dysfunction in middle-aged/older men with lower testosterone. Authors conclude that normal physiological levels of testosterone may be beneficial to cardiovascular health by attenuating the age-related decline in endothelial function.
Abstract
CONTEXT Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. OBJECTIVE We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. METHODS This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). CONCLUSION Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.
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Effectiveness of Exercise Training on Male Factor Infertility: A Systematic Review and Network Meta-analysis.
Hajizadeh Maleki, B, Tartibian, B, Chehrazi, M
Sports health. 2022;14(4):508-517
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Male factor infertility is characterised by the existence of suboptimal sperm parameters in the male partner of childbearing age and is presently defined as the inability to conceive a child with frequent and unprotected sexual intercourse in the fertile phase of the menstrual cycles for a year or longer. The main aim of this study was to evaluate the effectiveness of 1 or more of the selected types of exercise interventions (moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT)) in the prevention and treatment of male factor infertility. This study is a systematic review and meta-analysis of seven randomised controlled trials representing 18 groups (11 exercise, 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). Results show that in the setting of couples with male factor infertility, when compared with the NON-EX group, selected types of exercise interventions improved the relative risk of pregnancy rate in the following order: CET > MICT > RT > HICT > HIIT. The top-ranking interventions for live birth rate were for MICT, RT, HIIT, CET, and HICT. In addition, the interventions with the highest probability of being the best approach out of all available options in improving semen quality parameters were for CET, MICT, HICT, RT, and HIIT. Authors conclude that when clinicians are formulating clinical recommendations for preventing and treating male factor infertility, the findings of this study should be considered.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For couples with male factor infertility, this review recommends moderate intensity-aerobic exercise in combination with strength training to be the intervention with the highest probability of being the best approach for reproductive health benefits.
- A conservative interpretation of the findings is required because they were based on single studies.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The World Health Organisation estimates that infertility affects 10% to 15% of couples in industrialised countries. Approximately 50% of all infertility cases are attributed to male-related factors, in particular, poor semen quality (called male factor infertility). The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation.
Methods
This is the first study to undertake a systematic review with network meta-analysis of 7 RCTs to evaluate the effectiveness of 1 or more types of exercise interventions on male factor infertility and seminal markers of inflammation, as well as to provide clinicians with a ranking of treatments to inform them of the treatment effects of exercise training and physical activity.
The forms of exercise include: moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT).
7 RCTs representing 18 groups (11 exercise (supervised, not home-based), 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). All the RCTs were conducted in Iran involving healthy adult participants and/or infertile patients (with doctor-diagnosed male factor infertility). The intervention period was ≥10 weeks with a follow-up period.
None of the studies reported changes in either patients’ dietary intakes or normal daily physical activities and lifestyles during the intervention period.
Results
Compared with a non-intervention control group, the top ranking interventions:
For pregnancy rate:
Combined aerobic and resistance training (CET) (p= 0.89 relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (p=0.87, RR = 26.67), resistance training (RT) (p=0.61,RR = 12.54), high intensity continuous training (HICT) (p=0.34, RR = 5.55), and high-intensity interval training (HIIT) (p=0.28, RR = 4.63).
For live birth rate:
MICT (p=0.82, RR = 10.05), RT (p=0.70, RR = 4.92), HIIT (p=0.66, RR = 4.38)), CET (p=0.45, RR = 2.20), and HICT (p=0.30, RR = 1.55)
The following parameters/markers rank the 5 exercise strategies in order of effectiveness:
- Semen quality parameters were significantly improved after the following types of exercise interventions as compared with the non-intervention group [NON-EX]: CET > MICT > HICT > RT > HIIT
- The following training strategies were significantly better at improving seminal markers of oxidative stress: CET > MICT > HIIT > HICT > RT
- The following training strategies were significantly better at improving seminal markers of inflammation: CET > MICT > HIIT > RT > HICT
- The following training strategies were significantly better at improving measures of body composition and VO2 max: CET > HICT > MICT > HIIT > RT
- There was insufficient evidence of a difference for the selected types of exercise interventions versus NON-EX group for pregnancy and live birth rates in healthy participants.
Conclusion
Combined aerobic and resistance training (CET) was found to be the intervention with the highest probability of being the best approach for improving the male factor infertility.
Clinical practice applications:
- In light of these findings, it is reasonable to propose that infertile men and at-risk populations take part in the top-ranking interventions identified in this analysis.
- For substantial reproductive health benefits, one should consider doing all of the selected types of exercise interventions (CET, MICT, RT, HICT, and HIIT); however, moderate intensity-aerobic exercise and strength training in combination would generally be more favourable to lend clinically significant improvements.
- To add to this, exercise can offer a myriad of other health benefits, is a possibly safe activity and a cost-effective treatment strategy for male factor infertility.
Considerations for future research:
- There was only a small number of relevant trials available for comparison suggesting the need for additional study in this field.
- Further trials are needed to analyse the dose-response impacts of exercise modalities on male reproductive function.
- The results propose several domains for development in the reporting of RCTs addressing the impacts of interventional exercise studies on male reproductive function.
- Heterogeneity of some findings and discrepancy across the included studies was significant. For example, variations in the characteristics of training programs. Future analyses should aim to continue to address this.
- There is a concern that this study may not relate to already active patients with male factor infertility which future studies should address.
Abstract
CONTEXT Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. OBJECTIVE The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. DATA SOURCES We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. STUDY SELECTION A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. LEVEL OF EVIDENCE Level 1 (because this is a systematic review of RCTs). DATA EXTRACTION The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. RESULTS The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). CONCLUSION The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.
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The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
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9.
Comparison of L-Carnitine vs. Coq10 and Vitamin E for idiopathic male infertility: a randomized controlled trial.
Ma, L, Sun, Y
European review for medical and pharmacological sciences. 2022;26(13):4698-4704
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The World Health Organization (WHO) defines infertility as the inability to conceive after more than one year of regular unprotected intercourse. Male infertility has several different causes, ranging from genetic alterations to lifestyle choices to general medical diseases, medications, or even drugs. The aim of this study was to compare the efficacy of L-carnitine versus co-enzyme Q10 (CoQ10) and Vitamin E in improving outcomes in patients with idiopathic male infertility (asthenozoospermia [reduced sperm motility] or teratozoospermia [abnormal sperm morphology]). This study is based on the results of a randomised controlled trial which enrolled 143 patients with male infertility. Participants were randomly assigned to one of the two groups: intervention group (administered L-carnitine complex nutrient treatment) or the control group (administered CoQ10). Results show that: - after 3 months of treatment, sperm parameters improved with both L-carnitine and CoQ10 and vitamin E, except for sperm concentration with the latter. - comparing the two treatment modalities, the improvement was significantly better with L-carnitine as compared to CoQ10 and vitamin E for all three sperm parameters (concentration, progressive motility, and normal morphology). - a significant increase in the levels of testosterone and luteinizing hormone levels in patients on L-carnitine therapy, but only testosterone levels increased with CoQ10 and vitamin E. Authors conclude that future studies should examine clinical pregnancy rates in order to strengthen and warrant their findings.
Abstract
OBJECTIVE This study aimed at comparing sperm parameters and hormonal levels with L-carnitine vs. CoQ10 and Vitamin E therapy for patients with asthenozoospermia and teratozoospermia. PATIENTS AND METHODS A single-blind randomized controlled trial (RCT) was designed wherein patients were randomly allocated to receive L-carnitine complex nutrient treatment (study group - 15 g/bag, orally one bag at a time, twice a day) or CoQ10 (control group - 10 mg tablet orally, thrice daily) with Vitamin E (100 mg tablet orally, thrice daily) for three months. Outcome variables were sperm concentration, progressive sperm motility, normal sperm morphology, testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. RESULTS 143 patients were analyzed (73 in study and 70 in control group). Compared to baseline, sperm count, progressive sperm motility, and morphology improved significantly in the study group, but only progressive sperm motility and morphology improved in the control group. Serum testosterone levels significantly increased both in the study and control groups, while LH increased only in the study but not in the control group. All sperm parameters showed significantly better improvement in the study group, compared to the control group. Testosterone and LH levels were also higher in the study group compared to the control group. CONCLUSIONS L-carnitine significantly improves sperm motility, morphology, and concentration, while also improving testosterone and LH levels. Use of CoQ10 and Vitamin E resulted in improvement of only sperm motility, morphology, and testosterone levels. L-carnitine was found to be superior to the combination of CoQ10 and Vitamin E in improving sperm parameters. Further studies examining clinical pregnancy rates are needed to strengthen the evidence.
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Effect of vitamin E on Semen Quality Parameters: A Meta-Analysis of a Randomized Controlled Trial.
Wang, R, Wang, S, Song, Y, Zhou, H, Pan, Y, Liu, L, Niu, S, Liu, X
Urology journal. 2022;19(5):343-351
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The incidence of male infertility is increasing year by year. The mechanism of male infertility is complex. One of the important causes of male infertility is the decline in semen quality. The aim of this study was to evaluate the effectiveness of oral vitamin E in improving semen quality. This study is a meta-analysis of eight articles with a total of 459 patients, including 238 cases in the experimental group and 221 cases in the control group. Results show that oral vitamin E treatment could significantly increase the total sperm count and reduce the volume of semen. It was further found that oral vitamin E treatment for up to 6 months could improve the forward motility of sperm but not for 3 months. Authors conclude that vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients.
Abstract
PURPOSE To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted. MATERIALS AND METHODS The retrieval time was from January 1947 to May 2021, without language restriction. Stata 12.0 was used for the meta-analysis. RESULTS A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: - 0.55 to - 0.06, SMD = - 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001). CONCLUSION Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.