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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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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.
Muehlenbein, M, Gassen, J, Nowak, T, Henderson, A, Morris, B, Weaver, S, Baker, E
American journal of men's health. 2023;17(2):15579883221130195
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A growing body of research finds that in men, testosterone levels may be prognostic of clinical outcomes related to coronavirus disease 2019 (COVID-19 disease). The presence of pre-existing chronic conditions in many patients with COVID-19 disease further complicates the relationship among testosterone and severe outcomes. The aim of this study was to examine whether pre-existing conditions for severe COVID-19 disease were related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This study obtained data from men (n = 142) who participated in the longitudinal study Waco COVID Survey. All data included in the study was collected as part of the initial intake survey and first laboratory appointment. Results show that serum-free testosterone levels decreased as a function of age. In fact, greater burden of pre-existing conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. Furthermore, in men older than 40 years of age the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Authors conclude that their findings add important insights into the complex role of androgens in chronic and infectious diseases and contribute to the growing body of literature on the relationship between chronic disease and men’s testosterone levels.
Abstract
Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.
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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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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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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
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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Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.
Wang, T, Zhang, X, Zhou, N, Shen, Y, Li, B, Chen, BE, Li, X
Journal of the American Heart Association. 2023;12(11):e029512
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Dyslipidaemia is considered to be a risk factor for cardiovascular disease (CVD) and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to confer benefits for both dyslipidaemia and CVD, although results from clinical trials and meta-analyses (studies pooling data from smaller studies to increase statistical power) are mixed. The aim of this meta-analysis, using a particular statistical method, was to evaluate whether dose-response relationships may be non-linear. This meta-analysis included 90 randomised controlled trials with 72,598 participants overall. Lipids evaluated were triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and non-HDL cholesterol. A near linear relationship was seen between intake of combined EPA and DHA and a decrease in TG and non-HDL, both overall and for the subgroups of patients with and without hyperlipidaemia and overweight. For LDL and HDL, J-shaped relationships were seen, with an increase followed by a decrease with increasing EPA + DHA intake, both overall and in the subgroups with and without hyperlipidaemia. The authors also pooled data from studies which used the red blood cell omega index (a measure of omega-3 status) and found that with increasing omega-3 status, TG and non-HDL declined whilst HDL increased in a near linear fashion, whilst there was still a J-shaped curve for LDL. The authors consider that a medium dose of EPA + DHA may be needed for the management of dyslipidaemia, and a high dose for people at high risk of developing CVD.
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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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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The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Alshahrani, SM, Mashat, RM, Almutairi, D, Mathkour, A, Alqahtani, SS, Alasmari, A, Alzahrani, AH, Ayed, R, Asiri, MY, Elsherif, A, et al
Nutrients. 2022;14(21)
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The prevalence of cardiovascular disease increases as the modifiable risk factors increase, such as metabolic syndrome, obesity, type 2 diabetes, dyslipidaemia, and high blood pressure. Walnuts are a rich source of anti-inflammatory polyunsaturated fatty acids and omega-3 fatty acids. Walnuts are also known for their antioxidant properties and have been found to improve dyslipidaemia by reducing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). This systematic review and meta-analysis of thirteen randomised controlled trials evaluated the effects of walnut intake on lipid profile. Most of the included studies used walnut dosage ranging from 15 g to 99 g/day for six to sixteen weeks of intervention. The results of this systematic review and meta-analysis showed significant improvements in TC, LDL-c, and triglyceride (TG) levels. Subgroup analysis revealed greater improvement in TC, LDL-c, and TG in overweight and other comorbidities but had normal levels of TC and LDL-C. Additionally, female participants showed greater improvements in TG levels, followed by the walnut intervention. Intervention duration also affected the beneficial effect of the walnut intervention. Further robust studies are required to determine the effects of walnut intake on cardiovascular disease risk reduction due to the high heterogeneity between the included studies. However, healthcare professionals can use the results of this research to understand the benefits of including walnuts as part of a healthy diet and their impact on reducing dyslipidaemia.
Abstract
Cardiovascular diseases (CVD) are the leading causes of death worldwide. Dyslipidemia is a cardiometabolic risk factor of CVD, yet it can be modifiable. Walnuts have been suggested as a dietary intervention to improve the lipid profile. Therefore, we reviewed the literature to assess the evidence linking walnut intake to the improvement of blood lipids, including total cholesterol (TC), low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein (HDL-C) cholesterol, and triglycerides (TG). PubMed and Embase databases were searched from 2010 up to March 2022. We limited our search to randomized controlled trials conducted on humans and published in English during the specified period. Cochrane's risk of bias tool for interventional studies was used. A random-effects model was used for the meta-analysis, and weighted mean differences were obtained (WMD) Thirteen trials from the U.S., Europe, and Asia were included. Walnut intake was associated with significant reductions in TC (WMD: -8.58 mg/dL), LDL-C (WMD: -5.68 mg/dL), and TG (WMD: -10.94 mg/dL). Walnut consumption was not associated with HDL-C. Subgroup analysis showed that overweight/obese and those with comorbidities had more lipid improvement. A longer trial duration did result in further improvements. However, our results may be prone to bias due to extraneous confounding factors. Additionally, levels of heterogeneity were considerable for some outcomes of interest. Results from this meta-analysis provide evidence for the health benefits of walnuts on blood lipids. Walnuts possibly reduce the risk of CVD; thus, they can be successfully added to a dietary pattern to enhance health benefits.
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Effects of tart cherry juice consumption on cardio-metabolic risk factors: A systematic review and meta-analysis of randomized-controlled trials.
Moosavian, SP, Maharat, M, Chambari, M, Moradi, F, Rahimlou, M
Complementary therapies in medicine. 2022;71:102883
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Plain language summary
Cardiovascular disease (CVD) is a general term for disorders affecting the heart and blood vessels and is the number one cause of death world-wide. CVD risk factors include high blood pressure, high cholesterol, obesity, being overweight and diabetes. Tart cherry juice is a rich source of strong antioxidants such as proanthocyanidins, anthocyanins, and flavonols. These compounds have anti-inflammatory properties and are therefore potentially beneficial in CVD. The antioxidant potential of tart cherry juice has been extensively studied, but studies have shown contradictory results relating to the efficacy of tart cherry juice on cardio-metabolic risk factors. To date there is no meta-analysis looking at these effects. 10 RCTs were included and the results showed that cherry juice consumption led to a significant reduction in fasting blood sugar. However, there wasn’t any significant effect of cherry juice consumption on blood pressure, insulin, lipid profile levels, fat mass, and BMI. Further clinical trials using higher sample sizes are needed. The clinical importance of this study was that clinicians and nutritionists can recommend the consumption of tart cherry for the prevention and management of CVD related symptoms.
Abstract
BACKGROUND Tart cherries are rich in bioactive compounds, such as anthocyanins and other phytochemicals known to have antioxidant properties and exert cardiovascular protective effects. However, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of tart cherry juice consumption on cardio-metabolic risk factors. METHODS A systematic search was conducted on electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar from inception up to December 2021 to identify eligible RCT studies. A random-effect model was utilized to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). RESULTS Ten RCTs were included in the present meta-analysis. The pooled analysis revealed that tart cherry juice consumption led to a significant reduction in the fasting blood sugar (FBS) levels (WMD = -0.51 mg/dl [95% CI: -0.98, -0.06]). This lowering effect of FBS was robust in subgroups with cross-over studies, participants with age range ≥ 40, duration of follow-up ≤ 4 weeks, and baseline BMI ≥ 30. In contrast, tart cherry juice had no effect on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulin, body mass index (BMI), fat mass, systolic and diastolic blood pressure. However, in the subgroup analysis, some significant effects were observed for insulin, TG, TC, LDL-C, and HDL-C. CONCLUSION In summary, this meta-analysis showed that tart cherry juice mostly had a favorable effect on FBG levels. However, further RCTs with long-term intervention with different doses of administration are needed.
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Effects of Oat Beta-Glucan Intake on Lipid Profiles in Hypercholesterolemic Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Yu, J, Xia, J, Yang, C, Pan, D, Xu, D, Sun, G, Xia, H
Nutrients. 2022;14(10)
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Free full text
Plain language summary
Dyslipidaemia is one of the risk factors associated with cardiovascular disease. Beta-glucan is a viscous soluble fibre found in microalgae, fungi and grains like oats, barley, sorghum etc. This systematic review and meta-analysis included thirteen randomised controlled trials to evaluate the effectiveness of oat beta-glucans on the lipid profiles of patients with hypercholesterolemia. This research showed a significant reduction in total cholesterol and low-density lipoprotein levels in hypercholesterolemic adults after beta-glucan intake. However, beta-glucans did not impact triglyceride and high-density lipoprotein cholesterol. Beta-glucan's effect on lipid profiles depended on the severity of hypercholesterolemia, the duration of the intervention, the source of beta-glucan, and the dosage of beta-glucan. Healthcare professionals can use the results of this study to understand the lipid profile-improving effects of beta-glucans in adults with moderate hypercholesterolemia. However, further robust studies are required to evaluate the effects of beta-glucan on lipid profiles and how the effect is affected by gender differences.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Consumption of oat beta glucans may be beneficial for improving total cholesterol and LDL-c in people with mild and moderate hypercholesterolemia
- The U.S Food and Drug Administration (FDA) recommends 3g or more of oat beta glucans per day to reap the benefits. This could be from 90g of oats (3 x 30g portions) or 1 30g portion of oats, 3 oatcakes and 1-2 tbsp of oat bran.
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:
Authors highlight that Hypercholesterolemia is a risk factor for cardiovascular disease and a symptom of Metabolic Syndrome. Hypercholesterolemia commonly includes; elevated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-c) and lower levels of high-density lipoprotein cholesterol (HDL-c).
Conventional medical treatment for hypercholesterolemia is statins, however, statins can have a number of adverse side effects. For this reason, dietary interventions have been investigated including the use of oat beta-glucans for their potential lipid lowering effects.
The aim of this systematic review and meta-analysis was to synthesise and evaluate the evidence for the effects of oat beta-glucans on serum cholesterol and triglyceride (TG) levels in adults with hypercholesterolemia.
Thirteen randomised controlled trials (RCTs) published between 1999 – 2021 met the study inclusion criteria. These studies included a total population of 927 people aged between 38-76 years and from 7 different countries worldwide. The majority of participants were diagnosed with mild hypercholesterolemia.
Participants were randomised into an intervention group receiving dietary sources of oat beta-glucans or food with added oat beta-glucans or a placebo control group consisting of diets without beta-glucans.
Study lengths ranged from 3 to 8 weeks with doses of oat beta-glucans between 1.5g to 6g. The studies were also broken down into sub-groups for high and low doses of oat beta-glucan and mild and moderate hypercholesterolemia.
Baseline and endpoint cholesterol (total cholesterol C, HD-c & LDL-c) and triglycerides were used to assess the effectiveness of the interventions and a weighted mean difference (WMD) calculated with a 95% confidence interval (CI).
Key Findings:
- a reduction in total cholesterol (WMD = -0.24mmol/L; 95% CI)
- a reduction in LDL-c (WMD = -0.27mmol/L; 95% CI )
- Sub-groups found that oat beta-glucans reduced serum TG levels in patients with moderate hypercholesterolemia (WMD = -0.11 mmol/L; 95% CI) but not in cases of mild hypercholesterolemia. (WMD = -0.01 mmol/L; 95% CI)
- Higher daily doses of oat beta glucans had more positive effects on TG levels, however the results were not statistically significant in this meta-analysis
- <3g WMD -0.11 mmol/L; 95% CI: -0.13 to -0.08 mmol/L
- >3g WMD -0.00 mmol/L; 95% CI: -0.16 to -0.16 mmol/L
- Greater reductions in HDL -c were found in patients with moderate hypercholesterolemia (WMD-0.06 mmol/L; 95% CI; -0.07 to -0.05 mmol/L) compared to mild cases (WMD-0.01 mmol/L; 95% CI; -0.08 to -0.10 mmol/L).
Conclusion
Dietary intake of oat beta-glucans may support the reduction of total cholesterol and low density lipoprotein cholesterol, however, no significant changes were found for high density lipoprotein cholesterol or serum triglycerides. Due to the heterogeneity between studies and inconsistencies in results, more trials are needed with larger sample sizes and longer durations.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Based on the pooled results of this meta-analysis:
- 1.5g -6g of dietary intake of oat beta-glucans could support a reduction of TC and LDL-c in cases of mild and moderate hypercholesterolemia
- Intake of oat beta glucans >3g may reduce TG levels
- HDl -c may be improved with oat beta glucan intake of between 1.5g to 6g for clients with moderate hypercholesterolemia.
Considerations for future research:
The findings of 8 of the 13 RCTs indicated that when compared to the control group, LDL-c could be lowered by oat beta-glucans whilst the other 5 trials did not. However, the cumulative results of this meta analysis found a reduction in LDL-c.
There were also several limitations to this study:
- Heterogeneity between studies and inconsistent results
- Short study duration
- Small populations and limited sample size
- The results varied for different levels of hypercholesterolemia
- Results may also differ by sex and source of oat beta glucans
Larger and longer trials are therefore needed to confirm the results.
Abstract
(1) Background: hyperlipidemia is one of the cardiovascular diseases which becomes a great threat to the health of people worldwide. Oat beta-glucan is reported to have a beneficial effect on lowering blood lipids. To probe the effect of oat beta-glucan consumption on serum lipid profiles (total cholesterol, total triglyceride, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol), we carried out a systematic search on randomized controlled trials of oat beta-glucan intervention on hypercholesterolemic individuals. (2) Methods: the pieces of literature were obtained from PubMed, Scopus, Cochrane Library, Web of Science, and the Embase from inception to 28 February 2022. The results were presented with the weighted mean difference (WMD) with a 95% CI. The random-effects or fixed-effects model was applied according to the heterogeneity. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. (3) Results: thirteen trials with 927 participants were included in our meta-analysis. Overall, oat beta-glucan supplementation significantly reduced levels of TC (pooled WMD = -0.24 mmol/L; 95%CI: -0.28 to -0.20 mmol/L), LDL-c (pooled WMD = -0.27 mmol/L; 95%CI: -0.35 to -0.20 mmol/L). Furthermore, beta-glucan consumption did not show significant effects on TG (pooled WMD = -0.04 mmol/L; 95%CI: -0.13 to 0.05 mmol/L), HDL-c (pooled WMD = 0.00 mmol/L; 95%CI: -0.05 to 0.05 mmol/L). Subgroup analysis indicated that critical factors, such as disease severity of participants, the daily intervention of oat beta-glucan, source of oat beta-glucan, and duration of intervention had impacts on outcomes. (4) Conclusions: oat beta-glucan intake may significantly decrease the level of TC and LDL-c while no significant changes in TG and HDL-c were observed. This meta-analysis supports the health benefits of oat beta-glucan, especially for its cholesterol-lowering features, although it has some inevitable limitations.