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1.
Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease.
Yuan, S, Larsson, SC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023;21(2):398-405.e4
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The prevalence of non-alcoholic fatty liver disease (NAFLD) is projected to increase due to the obesity epidemic, rise in diabetes prevalence, and other factors. An inverse association between serum 25-hydroxyvitamin D [S-25(OH)D], a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies. The aim of this study was to determine the association between S-25(OH)D and NAFLD. This study is a 2-sample Mendelian randomisation study based on summary-level data of genome-wide association analyses on S-25(OH)D levels, NAFLD, and liver enzymes. Results show an inverse genetic correlation of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. Authors conclude that vitamin D may play a role in NAFLD prevention. However, further studies are needed in order to confirm the causal effect of NAFLD on lowering S-25(OH)D levels.
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Vegetarian and vegan diets and the risk of cardiovascular disease, ischemic heart disease and stroke: a systematic review and meta-analysis of prospective cohort studies.
Dybvik, JS, Svendsen, M, Aune, D
European journal of nutrition. 2023;62(1):51-69
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Cardiovascular disease (CVD) is mainly due to ischemic heart disease (IHD) and stroke. Plant-based diets are effective for improving CVD risk factors. This is further supported by the favourable cardiometabolic profile seen among vegetarians who predominantly exclude meat, fish and poultry from their diet, when compared to people consuming meat. The aim of this study was to analyse the association between vegetarian or vegan diets and risk of incidence and mortality from CVD, IHD and stroke, both overall and subtypes. This study is a systematic review and meta-analysis of thirteen prospective cohort studies. Results show a 15% and a 21% reduction in the relative risk of CVD and IHD, respectively, for vegetarians compared to nonvegetarians, but there wasn’t a clear association for total stroke or subtypes of stroke. Furthermore, an 18% reduction in the relative risk of IHD was observed among vegans when compared to nonvegetarians but the association lacked precision and no clear association was observed for CVD or stroke; however, there were few studies in the analyses of vegans. Authors conclude that their findings are consistent with existing guidelines recommending plant-based dietary patterns for CVD prevention. However, further studies are required to clarify the association between vegetarian diets and stroke risk, as well as the association between vegan diets and IHD.
Abstract
PURPOSE Vegetarian diets have been associated with reduced risk of ischemic heart disease (IHD). However, results regarding cardiovascular disease (CVD) overall and stroke are less clear. We conducted a systematic review and meta-analysis of prospective cohort studies on CVD, IHD and stroke risk among vegetarians or vegans versus nonvegetarians to clarify these associations. METHODS PubMed and Ovid Embase databases were searched through August 12, 2021. Prospective cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for incidence or mortality from CVD, IHD and stroke, comparing vegetarians and vegans to nonvegetarians were included. Risk of bias (RoB) was assessed using ROBINS-I and the strength of evidence was assessed using World Cancer Research Fund (WCRF) criteria. Summary RRs (95% CIs) were estimated using a random effects model. RESULTS Thirteen cohort studies (844,175 participants, 115,392 CVD, 30,377 IHD, and 14,419 stroke cases) were included. The summary RR for vegetarians vs. nonvegetarians was 0.85 (95% CI: 0.79-0.92, I2 = 68%, n = 8) for CVD, 0.79 (95% CI: 0.71-0.88, I2 = 67%, n = 8) for IHD, 0.90 (95% CI: 0.77-1.05, I2 = 61%, n = 12) for total stroke, and for vegans vs. nonvegetarians was 0.82 (95% CI: 0.68-1.00, I2 = 0%, n = 6) for IHD. RoB was moderate (n = 8) to serious (n = 5). The associations between vegetarian diets and CVD and IHD were considered probably causal using WCRF criteria. CONCLUSIONS Vegetarian diets are associated with reduced risk of CVD and IHD, but not stroke, but further studies are needed on stroke. These findings should be considered in dietary guidelines. REVIEW REGISTRATION No review protocol registered.
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3.
Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
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Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
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:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
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Time of the day of exercise impact on cardiovascular disease risk factors in adults: a systematic review and meta-analysis.
Sevilla-Lorente, R, Carneiro-Barrera, A, Molina-Garcia, P, Ruiz, JR, Amaro-Gahete, FJ
Journal of science and medicine in sport. 2023;26(3):169-179
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In humans, shifted sleep patterns seem to interfere with several metabolic pathways. Shift work, short sleep duration, exposure to artificial light, inadequate eating time window, and lack of physical activity, are some characteristics of the modern lifestyle that contributes to the occurrence and worsening of cardiovascular disease (CVD). The aim of this study was to analyse the time of the day of exercise-induced effects on CVD risk factors in adults. This study was a systematic review and meta-analysis of twenty-two studies. Results showed that exercise produces an acute reduction of systolic blood pressure independently of the time of the day at which it is performed. Similarly, exercise produces an acute increase in blood glucose independently of the time of the day. Authors concluded that further research is needed to establish whether there is a diurnal variation of exercise on cardiovascular health and how it is related to health status, sex, or the type of exercise.
Abstract
OBJECTIVES To compare the effect of a single bout of morning vs. evening exercise on cardiovascular risk factors in adults. DESIGN Systematic review and meta-analysis. METHODS A systematic search of studies was conducted using PubMed and Web of Science from inception to June 2022. Selected studies accomplished the following criteria: crossover design, acute effect of exercise, blood pressure, blood glucose, and/or blood lipids as the study's endpoint, a washout period of at least 24 h, and adults. Meta-analysis was performed by analyzing: 1) separated effect of morning and evening exercise (pre vs. post); and 2) comparison between morning and evening exercise. RESULTS A total of 11 studies were included for systolic and diastolic blood pressure and 10 studies for blood glucose. Meta-analysis revealed no significant difference between morning vs. evening exercise for systolic blood pressure (g ∆ = 0.02), diastolic blood pressure (g ∆ = 0.01), or blood glucose (g ∆ = 0.15). Analysis of moderator variables (age, BMI, sex, health status, intensity and duration of exercise, and hour within the morning or evening) showed no significant morning vs. evening effect. CONCLUSIONS Overall, we found no influence of the time of the day on the acute effect of exercise on blood pressure neither on blood glucose.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
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:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
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Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.
Hudson, J, Cruickshank, M, Quinton, R, Aucott, L, Aceves-Martins, M, Gillies, K, Bhasin, S, Snyder, PJ, Ellenberg, SS, Grossmann, M, et al
The lancet. Healthy longevity. 2022;3(6):e381-e393
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Hypogonadism is caused by testosterone deficiency and results in diminished sexual function, muscle wastage, weakness, osteoporosis, and reduced quality of life. Testosterone supplementation is used as a therapy for hypogonadism but there is some doubt on its safety, and it may come with serious side effects such as heart attacks. This systematic review and meta-analysis aimed to determine the effect of testosterone supplementation on heart health. The results showed that heart disease risk was unaffected by testosterone supplementation and there was a trend for fewer deaths following treatment. It was concluded that testosterone did not affect short-medium-term heart attack risk, however there was a lack of evidence in the long-term. This study could be used by healthcare professionals to understand that testosterone supplementation may be of benefit to individuals who need it without increasing their risk for heart attacks.
Abstract
BACKGROUND Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. METHODS We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. FINDINGS 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. INTERPRETATION We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. FUNDING National Institute for Health Research Health Technology Assessment Programme.
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8.
Psoriasis and cardiovascular disease risk in European and East Asian populations: evidence from meta-analysis and Mendelian randomization analysis.
Zhang, L, Wang, Y, Qiu, L, Wu, J
BMC medicine. 2022;20(1):421
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Psoriasis constitutes a chronic, inflammatory skin disease with an immune-genetic basis that has been linked to numerous diseases, including metabolic syndrome, cancer, as well as cardiovascular disease (CVD). The aim of this study was to determine if the relationship of psoriasis with CV events (CVE) risk is congruent with causal associations. This study is a report employing a meta-analysis of observational studies and a two-sample mendelian randomised trial (MR). Results from the meta-analysis show that psoriasis was remarkably associated with a higher risk of incident coronary artery disease (CAD) and myocardial infarction (MI) and was not associated with heart failure risk. Furthermore, the MR approach showed that psoriasis was linked with a higher risk of CAD in both European and East Asian populations. Additionally, psoriasis was also causally linked to an elevated risk of MI in European population. Authors conclude that their findings indicate a causal association of psoriasis with CAD and MI. However, further studies are needed to establish the mechanisms of the causal relationship of psoriasis with CAD and MI.
Abstract
BACKGROUND Psoriasis has been linked to cardiovascular disease (CVD), including coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF). However, available studies regarding this relationship have shown inconsistent results. Therefore, in this report, we performed a comprehensive review of the literature to assess the effects of psoriasis on risk of these CVDs. METHODS A search of literature until 24 December 2021 was done in PubMed, the Cochrane Library, Web of Science, Google Scholar, and Embase. Within European and East Asian populations, meta-analyses of observational studies assessing correlations between psoriasis and various CVD risk factors were conducted. Mendelian randomization (MR) was then employed to assess the causative impact of genetic pre-disposition for psoriasis on these CVD risk factors. RESULTS The results of the meta-analyses indicated that, in both the European and East Asian populations, psoriasis was significantly linked to an elevated risk in the incidence of CAD (RR = 1.51, 95% confidence interval (CI): 1.04-2.18, p = 0.028 and RR = 1.91, 95% CI: 1.62-2.25, p < 0.001) and MI (RR = 1.23, 95% CI: 1.04-1.46, p = 0.017 and RR = 2.17, 95% CI: 1.44-3.28, p < 0.001). A positive genetic relationship of psoriasis with CAD was found in European individuals (IVW OR1.03; 95% CI: 1.01-1.06, p = 0.005) and in East Asian individuals (IVW OR1.18; 95% CI: 1.03-1.32, p = 0.031). We also established that psoriasis was causally linked with an elevated risk of MI (IVW OR1.05; 95% CI: 1.01-1.09, p = 0.026) in the European population as determined using an MR approach. Moreover, our MR results were congruent with the null findings from the meta-analysis assessing associations of psoriasis with HF risk. CONCLUSIONS This research work provides preliminary evidence that psoriasis and CVD have a common genetic origin and that targeted psoriasis treatment might improve cardiovascular outcomes. These results not only increase our knowledge of the genetic underpinnings linking a comorbidity of psoriasis with CVD but also suggests a novel approach for CVD prevention.
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Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis.
Wen, W, Li, H, Wang, C, Chen, C, Tang, J, Zhou, M, Hong, X, Cheng, Y, Wu, Q, Zhang, X, et al
Frontiers in endocrinology. 2022;13:934225
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Non-alcoholic fatty liver disease (NAFLD) is a multi-system disease that not only affects the structure and function of the liver but also increases the incidence of type 2 diabetes, cardiovascular disease (CVD), cerebrovascular disease, and chronic kidney disease. In 2020, experts reached a consensus to recommend a more appropriate term to more accurately and positively define fatty liver disease associated with metabolic disorders, namely, metabolic dysfunction-associated fatty liver disease (MAFLD). The aim of this study was to investigate the risk of CVD incidence or CVD mortality in patients diagnosed with MAFLD. This study is a meta-analysis of ten cohort studies. Results show that patients in the MAFLD group had a significantly increased relative risk of CVD or death from CVD during the follow-up compared with the control group. Authors conclude that even though there is a positive association between MAFLD and the risk of CVD or death from CVD, further studies are needed to demonstrate different effects of the newly defined MAFLD on CVD compared with previous NAFLD.
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria. METHODS We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English. RESULTS By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01). CONCLUSIONS Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data.
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Efficacy of telemedicine for the management of cardiovascular disease: a systematic review and meta-analysis.
Kuan, PX, Chan, WK, Fern Ying, DK, Rahman, MAA, Peariasamy, KM, Lai, NM, Mills, NL, Anand, A
The Lancet. Digital health. 2022;4(9):e676-e691
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Digital health interventions (DHIs) have the potential to transform the diagnosis, monitoring, and management of chronic cardiovascular conditions. Many DHIs are widely deployed in health systems across the world, with adoption rapidly increasing in response to the coronavirus disease 2019 pandemic. The aim of this study was to provide an updated synthesis of evidence on the effectiveness of telemedicine in the management of cardiovascular diseases. This study is a systematic review and meta-analysis of seventy-two studies with a total of 127,869 participants, of whom 82,818 (65%) were males and 45051 (35%) were females. Results showed reduced cardiovascular-related mortality and hospitalisation for patients with heart failure who received combined remote telemedicine monitoring and consultation compared with usual care. Authors conclude that the findings of their study suggest a definite role for telemedicine in the management of heart failure, particularly in early treatment optimisation, but the value is less clear for long-term management strategy and other cardiovascular diseases. Thus, future research should focus to address the application of these technologies to unselected populations and longer-term effectiveness.
Abstract
BACKGROUND Telemedicine has been increasingly integrated into chronic disease management through remote patient monitoring and consultation, particularly during the COVID-19 pandemic. We did a systematic review and meta-analysis of studies reporting effectiveness of telemedicine interventions for the management of patients with cardiovascular conditions. METHODS In this systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane Library from database inception to Jan 18, 2021. We included randomised controlled trials and observational or cohort studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes for people either at risk (primary prevention) of cardiovascular disease or with established (secondary prevention) cardiovascular disease, and, for the meta-analysis, we included studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes and risk factors. We excluded studies if there was no clear telemedicine intervention described or if cardiovascular or risk factor outcomes were not clearly reported in relation to the intervention. Two reviewers independently assessed and extracted data from trials and observational and cohort studies using a standardised template. Our primary outcome was cardiovascular-related mortality. We evaluated study quality using Cochrane risk-of-bias and Newcastle-Ottawa scales. The systematic review and the meta-analysis protocol was registered with PROSPERO (CRD42021221010) and the Malaysian National Medical Research Register (NMRR-20-2471-57236). FINDINGS 72 studies, including 127 869 participants, met eligibility criteria, with 34 studies included in meta-analysis (n=13 269 with 6620 [50%] receiving telemedicine). Combined remote monitoring and consultation for patients with heart failure was associated with a reduced risk of cardiovascular-related mortality (risk ratio [RR] 0·83 [95% CI 0·70 to 0·99]; p=0·036) and hospitalisation for a cardiovascular cause (0·71 [0·58 to 0·87]; p=0·0002), mostly in studies with short-term follow-up. There was no effect of telemedicine on all-cause hospitalisation (1·02 [0·94 to 1·10]; p=0·71) or mortality (0·90 [0·77 to 1·06]; p=0·23) in these groups, and no benefits were observed with remote consultation in isolation. Small reductions were observed for systolic blood pressure (mean difference -3·59 [95% CI -5·35 to -1·83] mm Hg; p<0·0001) by remote monitoring and consultation in secondary prevention populations. Small reductions were also observed in body-mass index (mean difference -0·38 [-0·66 to -0·11] kg/m2; p=0·0064) by remote consultation in primary prevention settings. INTERPRETATION Telemedicine including both remote disease monitoring and consultation might reduce short-term cardiovascular-related hospitalisation and mortality risk among patients with heart failure. Future research should evaluate the sustained effects of telemedicine interventions. FUNDING The British Heart Foundation.