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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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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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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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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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Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.
Georgoulis, M, Yiannakouris, N, Kechribari, I, Lamprou, K, Perraki, E, Vagiakis, E, Kontogianni, MD
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022;18(5):1251-1261
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Obstructive sleep apnoea (OSA) represents one of the most common and serious sleep-related breathing disorders. Excess body weight has emerged as the strongest modifiable predictor of the onset and severity of OSA. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity. This study is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study, which was designed as a single-centre, single-blind, parallel, randomised, controlled clinical trial. Results show that respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Authors conclude that their findings indicate a dose-response relationship between the degree of weight loss and improvement in OSA severity and symptoms. However, further research is needed to gather more data on the optimal degree of weight loss and appropriate weight-loss interventions for managing the wide spectrum of OSA severity to guide clinical practice.
Expert Review
Conflicts of interest:
None
Take Home Message:
Important from a public health perspective:
- This study has confirmed that even a small degree of weight loss can have a beneficial effect on respiratory events and oxygen desaturation in moderate-to-severe OSA, but clinicians should preferably aim at a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
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
OSA represents one of the most common and serious sleep-related breathing disorders, with a high worldwide prevalence of almost 1 billion people. OSA has numerous well-established cardiometabolic consequences.
The authors highlight that weight loss is essential for obstructive sleep apnea (OSA) management. However, the optimal degree of weight loss for improving OSA severity or eliminating sleep-disordered breathing has not been extensively studied. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity.
Methods
This is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study. This study was designed as a single-center, single-blind, parallel, randomised, controlled clinical trial to evaluate the effectiveness of a weight-loss Mediterranean dietary/lifestyle intervention on managing OSA.
This 6-month long clinical trial included 180 adult, overweight/obese moderate-to-severe OSA patients (45 patients per study group plus a 29% dropout rate). All patients were prescribed the standard of care continuous positive airway pressure (CPAP) therapy and were randomised to 3 arms: standard care; Mediterranean diet; Mediterranean lifestyle
Based on percent change in weight at 6 months, participants were categorised into a weight-stable/gain (WS/GG) group or one of 3 weight-loss groups (WLG): < 5%WLG; 5%–10%WLG; ≥ 10%WLG. Polysomnographic data and OSA symptoms were also evaluated preintervention and postintervention.
Results
Results confirm a dose-response relationship between the degree of weight loss achieved through a dietary/lifestyle intervention and improvements in OSA severity.
- Respiratory events and oximetry indices improved only in patients who lost weight. Improvements were proportional to the degree of weight loss.
- Median percent change in apnea-hypopnea index (AHI) was −11.7%, − 37.9%, and − 49.3% in the < 5%WLG, 5%–10%WLG, and ≥ 10%WLG, respectively (P < .001).
- Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use–adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23–0.87) in the 5%–10%WLG and 0.32 (0.17–0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22–0.82]).
- Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss.
- The dose-response relationship between weight loss and improvement in OSA severity was evident regardless of self-reported CPAP use.
Conclusions
The authors conclude that even a < 5% weight loss was sufficient for improvements in respiratory events and oximetry indices, but the prevalence of severe OSA reduced only after a ≥ 5% weight loss, and patients achieving a ≥ 10% weight loss exhibited the greatest benefits compared to weight-stable/gain patients.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- Clinicians should aim for a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
- Improvements after weight loss were significant even though a healthy body weight was not achieved.
Considerations for future research:
- The study sample consisted of predominantly male, overweight, otherwise healthy patients with moderate-to-severe OSA. Therefore, findings cannot be generalised to the whole OSA population and further research is required with broader, diverse, study samples.
- 6 months is a short duration period, therefore longer trials are required.
- Self-reported CPAP use by participants is a limitation of this study. Further robust analysis methods should be considered for future trials.
- Participants were advised to abstain from CPAP therapy for 2 days prior to the follow-up PSG but this was not evaluated or confirmed in this study and should be in future research.
Abstract
STUDY OBJECTIVES Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. METHODS This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. RESULTS Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. CONCLUSIONS Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.
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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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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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5.
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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Plain language summary
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.
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6.
Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.
Goldenberg, JZ, Day, A, Brinkworth, GD, Sato, J, Yamada, S, Jönsson, T, Beardsley, J, Johnson, JA, Thabane, L, Johnston, BC
BMJ (Clinical research ed.). 2021;372:m4743
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Plain language summary
Diet modification has long been recognised as a component for the treatment of diabetes. Diets low in carbohydrates have been extensively researched, as a diet for those with Type 2 Diabetes (T2D). This systematic review and meta-analysis aimed to determine the effect of low carbohydrate diets on T2D. The systematic review found 23 studies, including 1357 individuals, investigating the role of low carbohydrate diets on T2D outcomes. Low carbohydrate diet was defined as less than 130g of carbohydrate (less than 26% of calories from carbohydrate) for at least 12 weeks. Results reported at 6 months, found low carbohydrate diets were more effective than a normal diet at achieving diabetes remission. However, this effect diminished at 12 months, although longer term improvements were seen in blood lipids, weight loss and measures of prediabetes. It was concluded that individuals with T2D, eating a low carbohydrate diet for 6 months may reverse the disease. This study could be used by healthcare professionals to recommend a short-term low carbohydrate diet to individuals with T2D, to improve their chance of going into remission.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Type 2 diabetes remains a significant and worsening problem worldwide, despite many pharmaceutical developments and a global emphasis on glycemic control.
- This review highlights structured LCDs as a worthwhile option for the management and treatment of diabetes, providing an opportunity for Nutritional Therapy Practitioners to support clients in adopting evidence-informed, modifiable dietary and lifestyle changes for Type Two Diabetes.
Evidence Category:
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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:
- Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of cases.
- Previous randomised trials assessed low carbohydrate diets (LCDs) (<26-45% of daily calories from carbohydrate) as encouraging to improve blood glucose control and outcomes of type 2 diabetes but did not systematically assessed remission of diabetes using low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes.
- Systematic reviews (SR) and meta-analyses represent the most valuable, reliable, and objective tool to summarise evidence from primary studies.
- This SR assessed 23 randomised controlled trials comparing LCDs with mostly low fat control diets in individuals / subjects / participants with type 2 diabetes. LCDs were defined as diets with less than 130 g/day or less than 26% of calories from carbohydrates, based on 2000 kcal/day. The authors used the Cochrane Risk of Bias tool 2.0 (RoB 2) to assess methodological quality of evidence, GRADE to assess the certainty of evidence
- On the basis of assessment of moderate to low certainty evidence, individuals / subjects / participants adhering to a LCD for six months may experience remission of type 2 diabetes without adverse consequences.
- Primary outcomes of interest were remission of type 2 diabetes (dichotomously defined as HbA1c <6.5% or fasting glucose <7.0 mmol/L), with or without the use of diabetes medication.
- Eight studies reported on remission of diabetes at six months. Pooled analysis showed that when remission was defined by an HbA1c level below 6.5% independent of medication use, LCDs increased remissions by an additional 32 per 100 patients followed (risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264; GRADE=moderate)
- When remission was defined by an HbA1c level below 6.5% and the absence of diabetes medication, LCDs increased remissions at a lower rate (risk difference 0.05, –0.05 to 0.14; 5 studies, n=199; GRADE=low)
- Additional primary outcomes were weight loss, HbA1c:
- 18 studies reported on Weight loss results (mean difference –3.46, 95% confidence interval –5.25 to –1.67; n=882 (note that positive results not sustained at 12 mo)
- Seventeen studies reported on HbA1c levels at six months, LCDs achieved greater reductions in HbA1c than did control diets (mean difference –0.47%, –0.60 to –0.34; n=747
- Limitations of study: 1) the definition of remission of diabetes, 2) Self-reported dietary intake data are prone to measurement error, particularly in dietary trials in which participants are not blinded
- This SR was funded in part by Texas A&M University.
- The authors declared no conflicts of interest.
Clinical practice applications:
The Authors highlight LCD diets incorporating carbohydrate of less than 130 g/day or less than 26% of calories (based on 2000 kcal/day) may be a safe strategy to help individuals with type 2 diabetes achieve weight loss and better blood glucose control over a six-month period. Results may not be sustained at 12 months.
Considerations for future research:
- The definition of diabetes remission needs clarification, especially with regard to threshold concentrations of Hb1Ac or fasting glucose and the use of diabetes medication.
- Safety concerns have been raised with LCDs. Although no significant or clinically important increase in total or serious adverse events was identified in this SR, these outcomes should be reported in future trials to confirm the certainty of evidence for safety.
- The Authors suggest long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes.
- Larger treatment effects for LCDs in shorter term trials (3 to <6 months), may be trialed as an effect modifier
Abstract
OBJECTIVE To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN Systematic review and meta-analysis. DATA SOURCES Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020161795.