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1.
The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.
Mardon, AK, Leake, HB, Hayles, C, Henry, ML, Neumann, PB, Moseley, GL, Chalmers, KJ
Reproductive sciences (Thousand Oaks, Calif.). 2023;30(2):390-407
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Endometriosis is a gynaecological condition with symptoms of pelvic pain, fatigue, and stress. Decreased quality of life, impaired fertility and hinderances to carry out day to day tasks are all associated with endometriosis. Treatment options involve medications and surgery; however, both are associated with poorer outcomes than the initial disease itself. Self-management strategies that the individual can perform themselves, such as lifestyle changes, meditation, and rest have all been used to improve the quality of life of individuals with endometriosis, however their effectiveness has not been determined. This systematic review and meta-analysis aimed to determine the effectiveness of self-management strategies for the management of endometriosis. The study showed that many self-management strategies were no more effective than placebo or hormonal therapies for the management of endometriosis. It was concluded that many self-management strategies were no more effective than hormonal treatment at reducing endometriosis symptoms and the studies that did show a benefit were insufficient to base recommendations on due to poor design. This study could be used by healthcare professionals to understand that currently the research on self-management strategies of endometriosis is poor and whilst some may be of benefit to individuals who cannot or do not want to take hormone therapy, more research is warranted.
Expert Review
Conflicts of interest:
None
Take Home Message:
It is not possible to generalise the findings of this systematic review for the self-management of endometriosis due to the poor quality of evidence. Further studies of higher quality are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
Endometriosis is an inflammatory condition where endometrial-like tissue is found outside of the uterus. Diagnosis of endometriosis is made in around 6-10% of females of reproductive age. Endometriosis can adversely affect fertility, psychological well being and quality of life (QoL). Conventional interventions can have side effects and limited effectiveness. The aim of this systematic review (SR) was to evaluate the efficacy of self-management interventions for pain-related symptoms and QoL.
Methods
Fifteen experimental studies were included in this SR. Ten evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter (OTC) medication, and one evaluated exercise. Outcome measures were self-reported for dysmenorrhoea, dyspareunia, overall pain, non-menstrual pelvic pain, use of medications and QoL.
Results
- Most dietary supplements were no more effective than placebo or frequently recommended medical interventions, at reducing pain-related outcomes.
- Melatonin (one RCT n=30) performed better than placebo for managing dysmenorrhoea and overall pain but not for non-menstrual pelvic pain. PEA-transploydatin (one RCT n=20) performed better than placebo for dysmenorrhoea and non-menstrual pelvic pain but not better than medical intervention.
- Resveratrol (one RCT n=22 & one intervention study n=12) plus the oral contraceptive pill (OCP) was more effective than the OCP alone for managing dysmenorrhoea.
- In one observational study, 75% of participants (n=295) reported a reduction in ‘high’ intensity pain scores following a 12-month gluten-free diet (p- value =<0.005). Similarly, a full dietary modification (one non randomised controlled trial , n=30) found less participants reporting pain at ‘high intensity’ (18%) compared to linseed and calcium oil supplements (41%) and placebo (62%).
- A metal trace element supplement was more effective than placebo for managing overall pain (one RCT p- value<0.001).
- Naproxen (one cross over trial, n=11) performed better than placebo at managing dysmenorrhoea (83% vs 41%, p- value 0.008).
- Hatha yoga (one RCT n=12) was found to be effective at reducing overall pain and improving QoL compared to no yoga (p-value <0.05).
Conclusion
Due to limited, low-quality evidence, high risk of bias and high levels of heterogeneity between studies, it was not possible to generalise the findings of the studies included in this systematic review. Further research of high-quality is needed in order to make self-management recommendations for females with endometriosis.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Evidence-based self-management interventions are considered critical for the management of endometriosis. However, the quality of evidence in this SR was considered of poor quality. Further high-quality research is needed in order to be able to make recommendations. Strategies that showed potential benefits included:
- Dietary modifications and a gluten-free diet may be effective for reducing the intensity of pain associated with endometriosis.
- Hatha yoga may be effective at reducing overall pain and supporting psychological wellbeing and QoL.
Considerations for future research:
High quality studies are needed as well as a ‘gold standard’ definition for self-management criteria. Understanding potential barriers to self-management interventions may also be beneficial.
Abstract
Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
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2.
The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.
Naseri, K, Saadati, S, Ghaemi, F, Ashtary-Larky, D, Asbaghi, O, Sadeghi, A, Afrisham, R, de Courten, B
European journal of nutrition. 2023;62(2):543-561
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When acute, inflammation is a necessary function of the immune system allowing the body to recognise and remove foreign stimuli. However, when chronic inflammation occurs, it can contribute to and exacerbate diseases such as type 2 diabetes (T2D). The gut microbiota and the use of probiotics has been shown to modulate processes within the body and decrease chronic inflammation, however research has not consistently shown this and an inverse relationship has been shown in some studies. This systematic review and meta-analysis aimed to determine the effect of probiotics and synbiotics on inflammation in individuals with prediabetes and T2D. A total of 32 randomised control trials were included in the meta-analysis and showed that certain, but not all inflammatory markers were reduced. Antioxidants were increased. The effect was especially pronounced in individuals with T2D as opposed to prediabetes. It was concluded that probiotics or synbiotics could be useful for individuals with T2D to reduce inflammation and reduce the risk for other associated diseases such as heart disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Probiotic and synbiotic supplementation may significantly reduce inflammation and oxidative stress, potentially lowering the risk of cardiovascular diseases in those with prediabetes and T2DM.
- These supplements may be particularly beneficial for individuals with T2DM and those who are overweight or obese.
- Incorporating probiotics and synbiotics into the diet could be a supportive strategy for improving metabolic health markers.
- The observed benefits vary depending on the type and duration of supplementation, suggesting that consistent, long-term use might be necessary to achieve noticeable health improvements.
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
This systematic review meta-analysis and meta-regression assessed the impact of probiotics and synbiotics on inflammation, antioxidants, oxidative stress, and adipokines in prediabetes and type 2 diabetes.
Methodology
The methodology involved searching PubMed/MEDLINE, ISI Web of Science, Scopus, and Cochrane Library databases without date or language restrictions until March 2022. Study quality was evaluated.
- Inclusion criteria: Adults 18+ with prediabetes or type 2 diabetes; interventions with probiotics or synbiotics versus placebo or other treatments; and reporting on inflammatory biomarkers, adipocytokines, and oxidative stress serum biomarkers in RCTs with parallel or cross-over designs.
Results
32 RCTs with 2074 participants were analysed, mostly in Asia (26 studies) and 5 in Europe, Africa, Oceania, and America, over 4 to 24 weeks. Dosages varied, including synbiotic bread with Lactobacillus sporogenes and inulin (1×10^8 CFU, 0.07g/g, thrice daily), 300ml/day fermented milk with L. helveticus, daily synbiotic and probiotic tablets, a probiotic mixture (120g/day), synbiotics (9g, thrice daily), multistrain probiotic yoghurt (300g/day), L. sporogenes-enriched bread (40g, thrice daily), and probiotic honey (2500mg/day). Measurements included CRP (31 RCTs), TNF-α (12 RCTs), GSH (13 RCTs), MDA (12 RCTs), TAC (11 RCTs), and NO levels (8 trials).
Effects of probiotics and synbiotics:
- significantly reduced CRP levels (-0.62 mg/L, 95% CI: -0.80 to -0.44, p < 0.001, 31 RCTs), showing greater efficacy in T2DM than prediabetes, particularly in individuals with overweight.
- TNF-α levels decreased in participants with T2D or overweight (-0.48 pg/mL, 95% CI: -0.81 to -0.15, p = 0.004, 12 RCTs).
- GSH levels significantly rose (69.80, 95% CI: 33.65 to 105.95, p < 0.001, 13 RCTs), independent of trial duration or baseline BMI.
- MDA levels were significantly reduced (-0.51, 95% CI: -0.73 to -0.30, p < 0.001, 12 RCTs) in studies lasting ≥12 weeks.
- TAC significantly increased (73.59, 95% CI: 33.24 to 113.95, p < 0.001, 11 RCTs), with more pronounced effects in longer trials and with probiotics.
- NO levels improved significantly (7.49, 95% CI: 3.12 to 11.86, p = 0.001, 9 trials) in individuals with obesity.
- Positive impacts on CRP, TNF-α, MDA, and TAC were more marked in trials ≥12 weeks.
Conclusions
Probiotic or synbiotic intake may benefit those with prediabetes and T2DM, reducing CRP, TNF-α, MDA, and enhancing TAC, GSH, NO levels, especially in T2DM individuals. Effects are stronger in individuals with overweight or obesity.
Clinical practice applications:
- Probiotic and synbiotic supplementation could be recommended to reduce inflammatory biomarkers like CRP and TNF-α, especially in individuals with T2DM.
- The improvements in oxidative stress markers, such as increased TAC and GSH and decreased MDA, support the use of probiotic and synbiotic supplements in managing oxidative stress in T2DM and prediabetes.
- Longer durations (≥12 weeks) of probiotic or synbiotic supplementation may offer a more pronounced effect on antioxidant capacity.
- The findings can guide personalised nutritional recommendations, as for example improvement in inflammation biomarkers and NO were more evident in individuals with T2DM or overweight suggesting an anti-inflammatory effect primarily in these groups. Moreover, markers related to antioxidant capacity were improved in those diagnosed with prediabetes or T2DM irrespective of BMI.
Considerations for future research:
- The beneficial effects on inflammatory and antioxidant/oxidative stress markers suggest a need for larger and longer-term studies to solidify the role of probiotics and synbiotics in benefiting chronic conditions like T2DM and prediabetes.
- There is potential for investigating the specific strains of probiotics that are most effective, considering varying outcomes observed across different studies.
- Research could explore the mechanisms by which probiotics and synbiotics exert their beneficial effects, contributing to a better understanding of gut-health interactions.
- The varying responses based on BMI categories indicate a need for personalised nutrition research to optimise probiotic therapy for individual needs.
- Future studies should consider standardising the dosage and formulation of probiotics to determine the most effective therapeutic doses and combinations.
Abstract
PURPOSE Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM). METHODS We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome. RESULTS A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels. CONCLUSION A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.
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3.
Effect of Chamomile on the Complications of Cancer: A Systematic Review.
Maleki, M, Mardani, A, Manouchehri, M, Ashghali Farahani, M, Vaismoradi, M, Glarcher, M
Integrative cancer therapies. 2023;22:15347354231164600
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Cancer and its treatments are associated with a wide range of complications such as mucositis, nausea/vomiting and dermatitis as well as implication for mental health, such as anxiety and depression, which can reduce quality of life (QOL) of patients. Chamomile is a commonly used medicinal herbal that is used in various forms orally and topically. The aim of this systematic review was to evaluate the effectiveness of chamomile, in its various forms of administration, for complications of cancer (any type) and its treatments. 18 controlled intervention studies including 1099 patients were included in the review. Due to the heterogeneity of the studies a meta-analysis was not possible. Benefits were reported for locally applied forms of chamomile for prevention of mucositis (7 of 8 studies), topical application for prevention of dermatitis or phlebitis (4/5), aromatherapy massage for anxiety (2) and QOL (2), tea for depression but not anxiety (1). No effect was seen of syrup for QOL (1). No side effects were reported in the included studies. The authors conclude that chamomile is a safe method to help mitigate the suffering from cancer complications.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Oral use of chamomile infusion may be helpful for people receiving treatment for cancer.
- Studies of this intervention report no safety concerns.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
This systematic review examined the use of chamomile in the support of people receiving treatment for cancer. Studies of a variety of chamomile preparations were considered.
Methods
- The authors retrieved 2240 studies from 5 on-line databases, from which 18 studies met the inclusion criteria for analysis.
- Fifteen of these studies were randomised control trials (RCT), three were non-randomised studies. German (Matricaria recutita) and Roman (Chamaemelum nobile) chamomile varieties were included. Studies using blends with other herbs were excluded.
- A narrative review was produced due to heterogeneous patient groups, preparations and trial protocols.
Results
- 1099 patients were included in the analysis, 57% female.
- Risk of bias assessment of 15 RCTs identified 2 RCTs with high risk of bias in blinding or in reporting outcome data.
- Studies in several cancer types were included, four in head and neck cancer (HNC), four in leukaemia, three in breast cancer, one in digestive system cancers, remaining in mixed cancer types.
- Eight studies reported the impact on oral mucositis of chamomile infusions used as mouthwash, or ice chips, or applied as an oral gel. Patients were receiving chemotherapy orstem cell transplantation, with interventions for up to 21 days after chemotherapy. Seven studies reported reduced severity and/or duration of mucositis and associated pain. One study of 14 days’ use after 5-fluorouracil treatment for colorectal cancer showed no impact on oral mucositis.
- One of three studies of psychological impact of cancer treatment used chamomile tea and reported no impact on anxiety but decreased depression. In comparison, two studies of weekly aromatherapy massage using chamomile oil reported reduced anxiety.
- One RCT in children with acute lymphoblastic leukaemia reported increased neutrophil count with 125mg chamomile in syrup versus placebo (p=0.019, 955 CI 15.076-171.324)
- One RCT in breast cancer randomised 45 women receiving usual antiemetics to additional chamomile capsules (500mg) or ginger (500mg) capsules, twice daily for 5 days before and after chemotherapy, or control group of no additional botanicals. Both botanical interventions reduced frequency of vomiting compared with the control group. Frequency of nausea was also reduced by ginger but not by chamomile.
- Five studies evaluated external treatments of chamomile on skin complications of radiotherapy. Reduction in radiation dermatitis in HNC patients with compresses soaked in chamomile infusion was reported.
- No side effects of using chamomile preparations were reported by the studies included in the systematic review.
Conclusion
Chamomile has been studied in a variety of preparations for people receiving treatment for cancer. Several RCTs reported significant amelioration of common side effects of cancer treatments, with reduced severity and/or duration of oral mucositis and associated pain.
Clinical practice applications:
- Chamomile infusion used in the mouth, as mouthwash or ice chips, may be useful for oral mucositis, a common side effect of cancer treatment
- Chamomile infusion may also be considered for mental wellbeing
- Several protocols for using chamomile preparations are described in the review and practitioners may refer to the individual studies cited
- This use of chamomile in the described applications appears to be safe
- (Reviewer’s note: allergy to ragwort would be a contraindication for use of chamomile preparations)
Considerations for future research:
- More detailed comparisons of chamomile preparations would be useful, for use in oral mucositis
- Topical applications may be studied further by researchers in aromatherapy.
Abstract
BACKGROUND AND OBJECTIVES Despite significant advances in the diagnosis and treatment of cancer, many people across the world still suffer from this chronic disease and its complications. Chamomile as an herbal medicine has gained an increasing attention for relieving cancer complications. This study aimed to integrate and synthesize current international evidence regarding the effect of chamomile on cancer complications. METHODS A systematic review was undertaken. Five online databases including Web of Science, PubMed [including MEDLINE], Cochrane Library, Scopus, and Embase were searched and articles published from inception to January 2023 were retrieved. All clinical trials and similar interventional studies on human subjects examining the effects of chamomile on cancer complications were included in the review and research synthesis. Relevant data were extracted from eligible studies after quality appraisals using proper methodological tools. The review results were presented narratively given that meta-analysis was impossible. RESULTS A total of 2240 studies were retrieved during the search process, but 18 articles were selected. The total sample size was 1099 patients with cancer of which 622 participants were female. Fifteen studies used an RCT design. Various forms of chamomile were used such as mouthwash, topical material, tea, capsule, syrup and aromatherapy massage. Chamomile effectively reduced oral mucositis, skin complications, depression, and vomiting and also improved appetite and quality of life among cancer patients. CONCLUSION The use of chamomile as a non-pharmacologic and safe method can be helpful for mitigating cancer complications in patients with cancer. Therefore, it can be incorporated into routine care along with other therapeutic measures to reduce patients' suffering related to cancer. SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO): CRD42022307887.
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4.
The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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5.
Impacts of Consumption of Ultra-Processed Foods on the Maternal-Child Health: A Systematic Review.
de Oliveira, PG, de Sousa, JM, Assunção, DGF, de Araujo, EKS, Bezerra, DS, Dametto, JFDS, Ribeiro, KDDS
Frontiers in nutrition. 2022;9:821657
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Ultra-processed foods (UPFs) are foods of little or no nutritional quality and often contain high amounts of saturated fat, trans fats, salt, additives, preservatives, colourings, and flavourings. These foods have become increasingly present in the diet of individuals who live in lower-middle, upper-middle, and high-income countries and may be part of the reason why several non-communicable diseases, such as obesity, type 2 diabetes, heart disease and cancer, are increasing. These foods may impact health at many stages in an individual’s lifecycle and in those who are pregnant increased consumption of UPFs may negatively affect both mother and child. This systematic review and meta-analysis aimed to determine the health impacts of UPFs on the health of mother and child. The results showed that higher dietary intake of UPFs was associated with gestational weight gain, early weaning, lower diet quality, alterations to metabolism in the baby and increased weight in the baby. It was concluded that UPF negatively affected nutrition and disease in the mother and child. There was a limited amount of research, however the quality was deemed quite high. This study could be used by healthcare professionals to recommend a high quality nutrient rich diet with limited UPFs during pregnancy.
Expert Review
Conflicts of interest:
None
Take Home Message:
- UPF contribute to >50% of dietary energy intake in high-income countries, and UPF may make up to 76% in some these countries.
- UPF consumption during pregnancy, lactation and childhood can be deleterious to gestational outcomes and infant and child health and development, by increasing the risk of several morbidities, in particular weight gain, metabolic changes and risk of NCDs. Excess weight gain in childhood increases the risk of related comorbidities and NCDs in adulthood, which may decrease life expectancy and lead to reduced schooling, a loss of productivity, and increased costs to the healthcare system.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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:
This systematic review aimed to summarise the consumption of Ultra-Processed Food (UPF) in pregnant and lactating women, and infants or children, and identify any associations with relevant health outcomes.
In informing their research question, the authors reference a marked increase in consumption of UPF in recent years, stating that consumption is estimated to count for >50% of energy intake in high-income countries such as the UK. They describe the literature associating UPF with non-communicable disease (NCD) risk, depression, and other morbidities in adulthood, as well as increasing evidence indicating negative associations during key developmental life stages such as the first 1,000 days, childhood, and adolescence.
Methodology followed standard robust systematic review procedures, including an assessment of quality. Of note; percentage of total energy from dietary UPF was defined by NOVA classification*.
From 7,801 hits, 15 studies (eight cohort and seven cross-sectional) were included in the final review; nine conducted in children <10 yr, five in pregnant women and one in lactating women. Fourteen of 15 studies were of high methodological quality.
UPF dietary contribution ranged from 15% to 76% with higher consumption rates reported in English children >1.5 yr, in whom 75% had an excessive free sugar intake. Overall, 12/15 studies found an association between UPF and negative health outcomes.
Pregnancy and lactation: positive associations or trends with: gestational weight gain, indicators of glucose metabolism, feelings of depression/sadness, neonatal adiposity, increased ADHD symptoms and reduced vitamin E status in lactation.
Childhood: positive associations or trends with: weight gain/BMI, waist circumference, fat mass, sugar intake, dental caries, wheezing and respiratory diseases, and urinary biomarkers of plastic compounds (phthalates and bisphenols). Dietary intake revealed increases in dietary energy, saturated fat, carbohydrates, total sugars and vitamin D, and a negative association with protein, polyunsaturated fats, sodium, zinc, vitamin A, folate and fibre.
Authors main conclusion: UPF consumption negatively affects dietary nutritional quality and health outcomes in pregnant and lactating women and their infants, and children. However, literature in this area is limited.
Strengths:
- Robust systematic review methodology.
- Registered protocol on PROSPERO (CRD42021236633).
- Assessment of quality of included studies.
- Subgroup analyses between the highest and lowest UPF consumption groups.
Limitations:
- Limited number of studies included.
- Exclusion of studies that did not assess dietary patterns using the NOVA classification, which may have missed other relevant articles.
- Only includes cross-sectional and cohort studies, which are prone to confounding and bias (Murad et al, 2016).
- Meta-analyses not attempted or not possible.
- No randomized controlled trials (e.g., assessing changes in response to reductions in UPF) included, and unclear from the review if such studies exist.
- Lacking a discussion on possible fortification of UPFs with vitamins and minerals that may be helpful to some population groups e.g., non-meat substitutes fortified with vitamin B12.
Funding: CAPES Foundation (Coordination for the Improvement of Higher Education Personnel in Brazil.
Conflicts of Interest: none declared
*The NOVA classification system was developed by researchers at the University of Sao Paulo, Brazil, and published in 2010. At that time, the term “ultra-processed foods” was a concept (FAO, 2019) that is now considered mainstream. NOVA classifies all foods into four groups according to the nature, extent and purposes of the industrial processes they undergo. The four groups are 1. Unprocessed and minimally processed foods; 2. Processed culinary ingredients; 3. Processed foods; 4. Ultra-processed foods.
References
FAO 2019. Ultra-processed foods, diet quality, and health using the NOVA classification system. Available at https://www.fao.org/3/ca5644en/ca5644en.pdf, accessed 22.07.2022
Murad MH, Asi N, Alsawas M, et al. New evidence pyramid. BMJ Evidence-Based Medicine 2016;21:125-127.
Clinical practice applications:
- UPF are ubiquitous in the food system, though many people may not be aware of the negative implications of their consumption.
- Education about UPF consumption and the risks associated should be provided, alongside recommendations and advice on how to adopt and maintain a more whole-foods dietary pattern. Education should refer to UPF available in the patient/client’s locality and include help with reading and interpreting food labels.
- In the cases of childhood overweight or obesity, ADHD or respiratory disorders, or during peri-conception, pregnancy and lactation, and especially where there is risk of excessive gestational weight gain, diabetes mellitus, hypertension, depression or risk of depression, UPF should be limited or avoided.
Considerations for future research:
- Evidence in this area is sparse.
- Robust, high quality clinical trials to assess the response on health outcomes to UPF reduction or avoidance, particularly at critical life stages, are warranted.
- In particular, research during the lactation period is lacking. No study was identified investigating the effect of UPF consumption on production and composition of breastmilk and development of specific nutritional deficiencies in infants.
Abstract
Background and Aims: Changes in eating patterns have been leading to an increase in the consumption of ultra-processed foods (UPF), negatively impacting the quality of the diet and generating risk of harm to the health of the adult population, however, there is no systematized evidence of the impact of UPF in maternal-child health. Thus, in this study we aimed to evaluated the association between UPF consumption and health outcomes in the maternal-child population. Methods: Systematic review registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021236633), conducted according to the PRISMA diagram in the following databases: PubMed, Medline, Scopus, Web of Science, Scielo, and CAPES thesis and dissertation directory. We included original cross-sectional, case-control and cohort studies in any language. Eligibility criteria were (a) food consumption assessment by the NOVA classification, (b) health outcome (nutritional or diseases), and (c) maternal-child population (pregnant, lactating women and infants/children). All data were analyzed and extracted to a spreadsheet structured by two independent reviewers. We evaluated the methodological quality of the studies included using the Newcastle-Otawa Scale and RoB 2. Results: Searches retrieved 7,801 studies and 15 contemplated the eligibility criteria. Most studies included were cohort studies (n = 8, 53%), had children as their population (n = 9, 60%) and only one study evaluated UPF consumption in infants and lactating women. Panoramically, we observed that a higher participation of UPF in children's diet has been associated with different maternal-child outcomes, such as increase of weight gain, adiposity measures, overweight, early weaning, lower diet quality, metabolic alterations, diseases, and consumption of plastic originated from packaging. Only one of the studies included did not present high methodological quality. Conclusion: Despite the limited literature on UPF consumption and health outcomes in the maternal-child population, the highest UPF consumption negatively impacted nutrition and disease development indicators in pregnant, lactating women and children. Considering the expressive participation of these foods in the diet, other studies should be conducted to further investigate the impact of UPF consumption on different health indicators, especially in the lactation phase for this was the one to present the most important knowledge gap. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236633], identifier [CRD42021236633].
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6.
Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Plain language summary
Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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7.
The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials.
Li, KP, Yang, XS, Wu, T
Frontiers in endocrinology. 2022;13:810242
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Plain language summary
Male infertility has gradually increased in recent years and is thought to be an equal contributor alongside female infertility in fertility issues. An imbalance in reactive oxygen species, which can damage sperm cells and the protective antioxidants is thought to be a major contributor to male infertility. This meta-analysis of randomised control trials aimed to determine which antioxidants have the most beneficial effect on sperm quality and count and pregnancy rates. The results showed that 10 antioxidants have been researched; L-carnitine (LC), L-carnitine+L-acetylcarnitine (LAC), coenzyme Q10 (Q10), omega-3 fatty acids (O-3), selenium (Se), zinc (Zn), vitamin E+vitamin C (VEC), folic acid (FAC), and N-acetylcysteine (NAC). LC was the most effective at improving sperm motility and morphology with reducing effectiveness for Q10, O-3, LAC, and Se. Four antioxidants improved sperm concentration starting with the most effective being 0-3, then Q10, Se, and LC. There were no effects of antioxidants on pregnancy rate. It was concluded that LC was the most effective at improving sperm motility and morphology and O-3 was the most effective at increasing sperm concentration, however this did not translate into improvements in pregnancy rate. This study could be used by healthcare professionals to understand that LC and O-3 may help to improve sperm quality and concentration, but this may not be sufficient to improve male fertility.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Consider antioxidant rich diets and increase awareness of the benefits of antioxidants and nutritional interventions in improving fertility rates
- Lifestyle modifications such as maintaining a healthy weight, regular exercise and avoiding harmful substances can enhance the positive effects of antioxidants on fertility
- Patients facing infertility should consider visiting a healthcare professional including nutritional therapists or fertility specialists
- Patients should approach interventions including antioxidant use with a long term perspective.
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 aim of this study was to investigate the impact of antioxidants on sperm quality parameters and pregnancy rates in cases of idiopathic male infertility. The focus was on randomised controlled trials (RCTs) to provide a comprehensive analysis of existing evidence.
Methods
- Utilized a network meta-analysis approach to synthesise data from 23 RCTs with 1917 patients and 10 different antioxidants
- Included studies with a diverse range of antioxidants and placebo/control groups
- Sample size varied across included studies, with a total number of participants analysed for each outcome.
Results
- L-Carnitine, L-carnitine+L-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more effective than placebo in improving sperm quality parameters
- L-Carnitine showed the most pronounced improvement in terms of sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%])
- ω-3 fatty acid had the most significant improvement in terms of sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml])
- None of these supplements showed a statistical significant improvement on pregnancy rates compared to placebo.
Conclusion
- L-Carnitine showed significant improvement in terms of sperm motility and morphology
- Omega-3 fatty acids significantly improved sperm concentration
- Co-Q10 has shown to effectively improve sperm motility and concentration
- No statistically significant result was observed in terms of pregnancy rate compared to placebo.
Clinical practice applications:
- Prescribing antioxidants should be considered for patients with idiopathic male infertility
- L-Carnitine can significantly improve sperm motility and morphology
- CoQ10 has shown to improve sperm motility and concentration
- Omega-3 improved sperm concentration
- Considering the patient’s needs, practitioners can tailor the antioxidant for most significant improvement and desired outcomes.
Considerations for future research:
- Investigate the synergistic effects of combining various antioxidants to improve sperm quality and pregnancy rates
- More studies to be conducted to assess the effect of antioxidant combinations on pregnancy outcomes
- Pharmacogenomics investigations could help tailor the interventions to provide individualised medicine
- Investigate the integration of antioxidant formulations with therapeutic interventions, lifestyle modifications, hormonal interventions etc.
Abstract
PURPOSE Male infertility is a global public health issue recognized by the WHO. Recently, antioxidants are increasingly used to treat idiopathic male infertility. However, the lack of available evidence has led to the inability to rank the effects of antioxidants on the sperm quality parameters and pregnancy rate of infertile men. This network meta-analysis studied the effects of different antioxidants on the sperm quality and pregnancy rate of idiopathic male infertility. METHODS We searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables, respectively, with 95% CIs. The outcomes were sperm motility, sperm concentration, sperm morphology, and pregnancy rate. RESULTS A total of 23 RCTs with 1,917 patients and 10 kids of antioxidants were included. l-Carnitine, l-carnitine+l-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more efficacious than placebo in sperm quality parameters. l-Carnitine was ranked first in sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%]). ω-3 fatty acid was ranked first in sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml]). In terms of pregnancy rate, there was no significant effect as compared with placebo. CONCLUSIONS l-Carnitine was ranked first in sperm motility and sperm morphology. ω-3 fatty acid was ranked first in sperm concentration. Coenzyme-Q10 had better effective treatment on sperm motility and concentration. Furthermore, high-quality RCTs with adequate sample sizes should be conducted to compare the outcomes of different antioxidants.
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8.
Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis.
Filippini, T, Wise, LA, Vinceti, M
Environment international. 2022;158:106920
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Plain language summary
Cadmium is a toxic metal released in the environment after both natural and anthropogenic activities, particularly in contaminated and industrial areas devoted to smelting and refining of metals, and the manufacturing of batteries, coatings, or plastics. Exposure to cadmium may occur through occupational activities, smoking, food, and air pollution. The aim of this study was to provide updated literature on cadmium exposure and the risk of both type 2 diabetes and prediabetes, and to model the shape of these associations using a dose response approach. This study is a systematic review and meta-analysis of forty-two studies. Diabetes was investigated as an outcome in thirty-one studies, prediabetes in four studies, and both diabetes and prediabetes in seven studies. Results show that higher cadmium exposure was associated with increased risks of both diabetes and prediabetes. Diabetes risk increased linearly in studies using urinary cadmium concentrations, while disease risk increased only at the highest exposure levels when assessed using blood concentrations. The analysis for prediabetes also showed a linear increase in risk from low exposure, with a flattening effect at higher urinary cadmium concentrations. Authors conclude that their findings add to the available evidence on potential adverse health effects of environmental exposure to cadmium.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Cadmium exposure through diet, occupational exposure and smoking may increase the risk of type 2 diabetes in affected individuals.
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:
Background
Cadmium exposure might occur through occupational activities, food, air pollution, and smoking. Smokers, in particular, have higher blood cadmium concentrations than non-smokers. Food is the main transmission route for non-smokers, particularly cereals, vegetables, mollusks, and offal. Females and older adults are at a greater risk due to an increased risk of iron deficiency in these population groups, leading to increased absorption, as well as greater age-related bioaccumulation.
Furthermore, cadmium exposure has been associated with an increased risk of diabetes in a number of studies, as referenced in the present manuscript. However, the magnitude and shape of the correlation are uncertain.This systematic review and meta-analysis therefore investigates the relationship between exposure to cadmium and type 2 diabetes and prediabetes risk.
Methods
- The systematic review was conducted and reported in line with the PRISMA 2020 statement. Search strings related to the terms “cadmium” and “diabetes”, or “prediabetes state” in PubMed/MEDLINE, Web of Science and EMBASE databases were employed to search for relevant articles. Latest search date: 1 October 2021.
- Eligibility criteria included: studies evaluating cadmium exposure via biomarker levels with outcomes of interest being type 2 diabetes or prediabetes using WHO criteria and the American Diabetes Association; and reporting of relative risk estimates using the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) with the corresponding 95% confidence interval (CIs). For inclusion in dose-response meta-analysis: reported effect estimates for all exposure categories along with dose in each category.
- Studies were assessed for risk of bias using theROBINS-E tool. Overall certainty of the evidence was assessed using the GRADE approach.
- The meta-analysis involved estimating RRs with corresponding 95% CIs from each study. Generalised least-squares regression with a random effects model and restricted maximum likelihood estimation were used. The highest versus lowest exposure categories were compared. The association between exposure and risk of diabetes or prediabetes was investigated using a one-stage dose-response meta-analysis. Sensitivity analyses were performed and heterogeneity between studies was assessed..
Results
- 42 eligible studies (case-control, cross-sectional, and cohort studies), ranging 65-34, 814 male and female adult participants, were identified investigating the association between cadmium exposure and risk of diabetes or prediabetes. Seven of the included studies were at overall high risk of bias; heterogeneity in the resulting meta-analyses was moderate to substantial. Sensitivity analyses indicated comparable results. Assessment with GRADE found no major inconsistency, indirectness or imprecision for either outcome.
- Comparing the highest versus lowest cadmium exposure concentrations associated with type 2 diabetes resulted in a RR of 1.24 (95% CI 0.96–1.59), RR 1.21 (CI 95% 1.00–1.45), and RR 1.47 (CI 95% 1.01–2.13) for blood, urinary, and toenail matrices, respectively. Concurrently, there was an elevated risk of prediabetes for cadmium levels in urine of RR 1.41 (95% CI: 1.15–1.73) and blood RR 1.38 (95% CI: 1.16–1.63), respectively.
- In the dose-response meta-analysis, a linear positive correlation between increasing urinary cadmium levels and diabetes risk was observed, with a RR 1.25 (95% CI 0.90–1.72) at concentration 2.0 µg/g of creatinine compared with no exposure. Conversely, for blood cadmium concentrations, the diabetes risk seemed to rise above 1 µg/L compared with no exposure. Moreover, prediabetes risk increased up to approximately 2 µg/g creatinine beyond which a plateau was reached with RR 1.40 (95% CI 1.12–1.76) at 2 µg/g creatinine.
- The meta-regression showed a negligible correlation between blood cadmium levels and diabetes risk. However, a positive yet imprecise association was found with increasing urinary cadmium concentrations. Similarly, no association was observed between blood cadmium concentrations and risk of prediabetes, whereas a positive relationship with urinary cadmium levels was observed. However, these findings were based on a limited cohort of studies.
Conclusions
- A positive linear correlation between cadmium concentration (measured in multiple matrices) and risk of both type 2 diabetes and prediabetes with a dose-response relationship (moderate-certainty evidence) were observed in this systematic review and meta-analysis. Diabetes risk increased linearly in studies using urinary cadmium concentrations, whereas disease risk increased only at the highest exposure levels when assessed using blood levels. The analysis for prediabetes also demonstrated a linear increase in risk from low exposure, which plateaued at higher urinary cadmium concentrations.
Clinical practice applications:
- To inform practitioners and clients of the risks of cadmium exposure in the diet, through occupational exposure, and through smoking.
- To motivate practitioners to educate themselves and their clients regarding the foods which may pose a higher risk of cadmium exposure (not reviewed in the present article).
- To advise clients on prediabetes and type 2 diabetes risk from cadmium exposure through smoking.
Considerations for future research:
- As cited by the authors, future studies could incorporate stratified analysis in specific subgroups, e.g., non-smokers, or could be restricted to prospective cohort studies with more sufficient data,
- Large-scale observational studies could be conducted investigating cadmium exposure in smokers versus non-smokers.
- Clinical trials could be performed to evaluate the effect of reduction or cessation of tobacco smoking on total body cadmium concentrations .
- Continuous surveillance of dietary cadmium exposure and other heavy metals should be prioritised to inform public health.
- Dietary interventions could assess the possibility to attenuate the risk of cadmium exposure.
Abstract
BACKGROUND Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. OBJECTIVE To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. DATA SOURCE After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. STUDY ELIGIBILITY CRITERIA We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. RESULTS In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. LIMITATIONS AND CONCLUSIONS This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
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9.
The association between vitamin D status and inflammatory bowel disease among children and adolescents: A systematic review and meta-analysis.
Fatahi, S, Alyahyawi, N, Albadawi, N, Mardali, F, Dara, N, Sohouli, MH, Prabahar, K, Rohani, P, Koushki, N, Sayyari, A, et al
Frontiers in nutrition. 2022;9:1007725
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Plain language summary
Vitamin D deficiency is often seen in children with inflammatory bowel disease (IBD). This meta-analysis of 35 different studies aimed to determine the relationship between blood vitamin D levels and IBD in children. The results showed that compared to healthy controls, individuals with IBD had slightly but not significantly lower vitamin D levels. It was unclear how different classifications of the disease i.e whether the disease manifests as diarrhoea, constipation, or a mixture of both, may affect vitamin D levels. The paper concluded that vitamin D levels may be slightly lower in children with IBD. This study can be used by healthcare professionals to understand that some children with IBD may have lower than normal vitamin D levels, however it does not provide justification to measure these without further clinical signs of deficiency.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Without further research, justification to measure vitamin D levels in children with IBD would require other clinical signs of deficiency.
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 aim of the study was to determine the relationship between serum vitamin D levels and paediatric inflammatory bowel disease (IBD).
Methods
- This systematic review and meta-analysis of 35 case-control, cross-sectional or cohort studies followed PRISMA and MOOSE guidelines
- Five different libraries were searched
- 4803 children were included with the majority from the United States, and the remainder from Australia, Finland, Denmark, Italy, South Korea, and Israel.
Results
- 16 studies were appropriate for meta-analysis and showed a trend of lower vitamin D levels in children with IBD compared to healthy controls, but this was not statistically significant (-1.159 ng/ml; 95% CI: -2.783, 0.464)
- 18 studies with 2602 children showed that the prevalence of vitamin D deficiency or insufficiency was 44% (95% CI: -0.34- 0.54)
- There was significant heterogeneity between the prevalence studies (P=<0.001; I2=97.31%) as they included children with different classifications of IBD such as ulcerative colitis and Crohn’s Disease and used different assessments of serum vitamin D levels
- A strength was that most studies included in the systematic review and meta-analysis were of high quality.
Conclusion
- There is a non-significant trend towards lower serum vitamin D levels in children with IBD.
Clinical practice applications:
- Practitioners could consider measuring serum vitamin D levels in children with IBD
- However, as vitamin D levels were not lower in children with IBD in the present paper, practitioners should be aware that lower vitamin D concentrations may be due to other factors
- Furthermore, heterogeneity in the study means that it is unclear as to how different forms of the disease may affect levels
- Vitamin D regulates the immune response and as this is an immune disease, a better understanding of levels may be beneficial.
Considerations for future research:
- Future research could consider the effect of supplementary vitamin D intakes on IBD symptoms.
Abstract
AIM: Vitamin D deficiency is very common among children with IBD. Since there are conflicting results regarding the association of vitamin D with IBD, we conducted this systematic review to confirm the association of vitamin D with IBD. METHODS We conducted a systematic search in Scopus, Cochrane Library, Web of Science, PubMed, and Google Scholar to find relevant studies. Articles with cross-sectional and case-control designs that reported the association between vitamin D and IBD among children were included. RESULTS Eventually, 9 studies (with 16 effect sizes) reported the mean and SD or the median and the interquartile range of serum vitamin D levels in both subjects with IBD and control subjects. The random effects meta-analysis revealed that subjects with IBD had -1.159 ng/ml (95% CI: -2.783, 0.464) lower serum vitamin D concentrations compared with their healthy counterparts, but this difference was not significant. A total of 14 studies (with 18 effect sizes) with 2,602 participants provided information for the prevalence of vitamin D deficiency or insufficiency in patients with IBD as 44% (95% CI: 0.34-0.54) with significant heterogeneity noted among studies (p < 0.001; I2 = 97.31%). CONCLUSION This systematic and meta-analysis study revealed that vitamin D deficiency was associated with IBD. Longitudinal studies should be conducted in the future to confirm our findings. Large randomized controlled trials assessing the doses of supplementation of vitamin D would provide a better understanding of the association between vitamin D and IBD.
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10.
Association between Allium vegetables and the risk of non-digestive tract cancer: A systematic review and meta-analysis of cohort and case-control studies.
Guo, L, Yuan, X, Yang, B, Tang, G, Liang, H, Guo, F
Cancer treatment and research communications. 2022;32:100598
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Allium vegetables, such as garlic, onion, and leeks, are characterized by a high content of organosulfur compounds, flavonoids, glutathione, selenium compounds, and vitamins E and C. The aim of this study was to clarify the role of Allium vegetables in non-digestive tract cancer. This study is a systematic review and meta-analysis of 5 studies (11 cohort and 14 case-control studies) on Allium vegetables involving 18,070 patients. Results showed that Allium vegetable consumption could reduce the risk of non-digestive tract cancer demonstrating the protective role of Allium vegetables. Authors conclude that further randomized controlled trials or well-designed cohort studies with high quality are needed to further confirm the findings of this study.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The findings of this meta-analysis suggest that allium vegetable consumption is correlated with a 14% decreased risk of non-digestive tract cancer
- Of the allium vegetables studied, onion and garlic were more likely to lower the risk of non-digestive tract cancer. Due to the limited under of eligible studies and small sample sizes, the authors of this study suggest that the impact of leeks on non-digestive cancers be interpreted with caution
- Allium vegetables appear to inhibit hepatocarcinogenesis, as well as the formation of nitrosamines. They also stress the endoplasmic reticulum and the death receptor pathway, hence reducing inflammation and modulating the immune system.
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:
- The purpose of this study was to evaluate the role of allium vegetable intake in non-digestive cancer prevention, such as lung, breast, ovarian and prostate
- This is a well-designed meta-analysis which was performed following PRISMA guidelines and included 11 cohort and 14 case-control studies of 18,070 patients
- The Newcastle-Ottawa Scale (NOS) was used to assess study quality. All included studies had NOS scores of >=7, indicating a lower risk of bias and better study quality.
Results
Overall, significant associations were found between higher Allium vegetable intake and lowered risk of non-digestive tract cancer (OR: 0.86; 95% Cl: 0.80-0.93) in a random-effects model.
When stratified:
- By study design, statistically significant effects were observed in cohort studies (OR; 0.78, 95% Cl: 0.69-0.90) but not case controlled studies (OR 0.94; 95% Cl: 0.87-1.02)
- By sex, statistically significant effects were observed in both women (OR: 0.89; 95% Cl: 0.81-0.98) and men (OR: 0.81, 95% Cl: 0.69-0.96)
- By allium vegetable type, onion (OR: 0.81, 95% Cl: 0.69-0.95) and garlic (OR: 0721, 95% Cl: 0.63-0.82) were more likely to have a lower risk of non-digestive tract cancer than leek (OR: 0.88, 95% Cl: 0.56-1.38)
- By study location, statistically significant correlation was found among studies in China (OR: 0731, 95% Cl: 0.57-0.94) but not Europe (OR: 0.93, 95% Cl: 0.85-1.02) or America (OR: 0.88, 95% Cl: 0.76-1.03)
- By cancer type, statistically significant risk decreases were seen with prostate cancer (OR: 0.81, 95% Cl: 0.69-0.96), marginal risk decrease with ovarian cancer (OR: 0.77, 95% Cl: 0.60-1.00), whilst no statistically significance was reached with breast cancer (OR: 0.94, 95% Cl: 0.83-1.05).
Limitations
- This meta-analysis included retrospective observational studies, which may introduce recall bias.
Clinical practice applications:
- Healthcare providers can use the results of this study to encourage the consumption of allium vegetables, in particular garlic and onion, to reduce the risk of non-digestive cancers, in particular prostate
- The results of this study could be used to encourage dietary variety, particularly in light of allium vegetables falling under the category of high-FODMAP foods. FODMAP dietary eliminations are not discussed in this paper.
Considerations for future research:
- To build on these findings, randomised-controlled trials or high quality cohort studies are needed.
Abstract
PURPOSE To clarify the role of Allium vegetables in non-digestive tract cancer, we conducted this meta-analysis. METHODS Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a meta-analysis of published studies assessing the associations between Allium vegetables and the risk of non-digestive tract cancer. We estimated the pooled odds ratio (OR) of non-digestive tract cancer for the highest and lowest Allium vegetable consumption using random-effects models. A dose-response regression model was used to evaluate the relationship between Allium vegetables and non-digestive tract cancer risk. RESULTS In a pooled analysis of 25 studies (11 cohort and 14 case-control studies) on Allium vegetables, a total of 18,070 patients with non-digestive tract cancer were finally included. Integrated OR of non-digestive tract cancer was 0.86 [95% confidence interval (CI):0.80-0.93] for the highest versus the lowest Allium vegetable consumption for all studies, 0.78 (95% CI:0.69-0.90) for case-control studies and 0.94 (95%CI: 0.87-1.02) for cohort studies. Sensitivity analysis showed that the pooled effect was stable. No apparent publication bias was identified in this study; however, the cumulative meta-analysis suggested that studies conducted earlier (from 1994 to 1997) might be a source of heterogeneity. Dose-response regression model indicated that Allium vegetable consumption was associated with the risk of non-digestive tract cancer (P = 0.001 for non-linearity; P = 0.032 for linearity). CONCLUSION Higher Allium vegetable consumption could reduce the risk of non-digestive tract cancers, demonstrating the protective role of Allium vegetables.