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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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Evidence of lifestyle interventions in a pregnant population with chronic hypertension and/or pre-existing diabetes: A systematic review and narrative synthesis.
Goddard, L, Patel, R, Astbury, NM, Tucker, K, McManus, RJ
Pregnancy hypertension. 2023;31:60-72
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Chronic hypertension complicates ≤5 % of pregnancies, and those entering pregnancy with a pre-existing diagnosis of diabetes has a global prevalence of between 0.5 % and 2.6 %. The aim of this study was to collate the evidence around lifestyle interventions during pregnancy for women with chronic hypertension and/or pre-existing diabetes (type 1 and type 2). This study is a systematic review and meta-analysis of nine randomised controlled trials. Results show lack of clarity and data on the effect of lifestyle interventions in pregnant women with chronic hypertension and/or pre-existing diabetes, thereby exposing key gaps in the literature. Authors conclude that there is a shortage of primary interventional studies examining the effect of lifestyle interventions in high-risk pregnant populations who enter pregnancy with chronic conditions.
Abstract
BACKGROUND Pregnant people with chronic hypertension, pre-existing diabetes or both are at high risk of developing cardiovascular disease. Lifestyle interventions play an important role in disease management in non-pregnant populations. AIM: To review the existing evidence of randomised controlled trials (RCTs) that examine lifestyle interventions in pregnant people with chronic hypertension and/or pre-existing diabetes. METHODS A systematic review and narrative synthesis was conducted. Five electronic databases were searched from inception to April 2021 for RCTs evaluating antenatal lifestyle interventions in people with chronic hypertension and/or pre-existing diabetes with outcomes to include weight or blood pressure change. RESULTS Nine randomised controlled trials including 7438 pregnant women were eligible. Eight studies were mixed pregnant populations that included women with chronic hypertension and/or pre-existing diabetes. One study included only pregnant women with pre-existing diabetes. Intervention characteristics and procedures varied and targeted diet, physical activity and/or gestational weight. All studies reported weight and one study reported blood pressure change. Outcome data were frequently unavailable for the subset of women of interest, including subgroup data on important pregnancy and birth complications. Eligibility criteria were often ambiguous and baseline data on chronic hypertension was often omitted. CONCLUSION A lack of primary interventional trials examining the effect of lifestyle interventions on weight and blood pressure outcomes in pregnant populations with chronic hypertension and/or pre-existing diabetes was evident. Lifestyle modification has the potential to alter disease progression. Future trials should address the ambiguity and frequent exclusion of these important 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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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 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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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 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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The Effect of Yoga on the Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Ghazvineh, D, Daneshvar, M, Basirat, V, Daneshzad, E
Frontiers in nutrition. 2022;9:942702
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Modernisation has brought increased comforts and limited mobility in our lives at the cost of an increased prevalence of hypertension, diabetes mellitus, dyslipidaemia, and obesity, which are predecessors of major cardiovascular diseases. Prevention and control of coronary heart disease and its associated diseases are essential and can be achieved by modifying the lipid profile. The aim of this study was to systematically assess the effects of yoga on blood lipid levels. This study is a systematic review and meta-analysis of fifty-three randomised controlled studies. All studies employed a parallel design with a total of 13,191 participants whom were divided into 6,700 individuals in the control group and 6,517 in the intervention group. Results show that yoga had decreased total cholesterol, low-density lipoprotein cholesterol, triglycerides, and very low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol among yoga practitioners. Authors conclude that yoga had a striking effect on balancing lipid profiles.
Abstract
OBJECTIVES Yoga is a mind-body stress-relieving exercise that increases mental and physical health, which may have a role in the improvement of metabolic disorders. The present study has reviewed the effect of yoga on lipid profiles as a systematic review and meta-analysis. METHODS We evaluated the available randomized controlled trials on the effects of yoga-based programs, and lipid profiles by searching PubMed/Medline, Scopus, Web of Science, and the Cochrane central register of control trials up to January 2022. Both fixed and random effect analyses were used to find the relationships. Subgroup analysis was performed based on the continent, duration of the included studies, gender, and health condition of participants to discover the sources of heterogeneity. RESULT Fifty-three studies were included in the current systematic review and meta-analysis with a total sample size of 13,191. There was a striking association between yoga and total cholesterol (-10.31 mg/dl; 95% CI: -14.16, -6.45; I 2 = 82.5%, P < 0.001), low-density lipoprotein cholesterol (-8.64 mg/dl; 95% CI: -12.03, -5.25; I 2 = 75.0%, P < 0.001), high-density lipoprotein cholesterol (1.98 mg/dl; 95% CI: 0.81, 3.14; I 2 = 91.6%, P < 0.001), triglycerides (-13.50 mg/dl; 95% CI: -20.09, -6.92; I 2 = 90.7%, P < 0.001) and very low-density lipoprotein (-3.94 mg/dl; 95%CI: -6.31, -1.56; I 2 = 72.2%, P < 0.001). CONCLUSION It seems yoga interventions had a substantial effect on lipid profiles, however, more qualified trials or cohort studies are needed to conclude exactly.
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Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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The effects of saffron supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.
Zamani, M, Zarei, M, Nikbaf-Shandiz, M, Gholami, F, Hosseini, AM, Nadery, M, Shiraseb, F, Asbaghi, O
Frontiers in nutrition. 2022;9:1055517
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Cardiovascular disease (CVD) is a leading cause of death and disability around the world and presents a significant burden for healthcare systems. CVD has many risk factors, including diet and lifestyle habits. Hence, favourable interventions in those areas can help prevent and manage CVD. This systematic review examined the effects of saffron crocus on cardiovascular risk factors. Saffron is derived from the flowering plant Saffron Crocus (Crocus sativus). It contains many active compounds such as crocetin, crocin, picrocrocin, and safrana, which in various studies demonstrated positive effects on blood glucose levels, insulin resistance and sensitivity and blood fats, besides also having antioxidant and anti-inflammatory qualities. Yet, results were not always consistent, and hence this meta-analysis gathered evidence from 32 randomised controlled trials (RCTs) which included a total of 1674 subjects and investigated the effect of saffron supplements on cardiovascular risk factors such as blood fats, blood glucose control, blood pressure, anthropometric measures, and inflammatory markers. In conclusion, the analysis showed that saffron supplementation aided the reduction of some inflammatory markers (CRP, TNF-α), had favourable effects on antioxidant capacity, reduced blood fats except high-density lipoprotein (HDL), enhanced blood control and insulin sensitivity, reduced blood pressure and was linked to a reduction in waist circumference but with no significant effect on weight itself, BMI or fat mass. The authors discussed how their results relate to previous research and what underlying mechanisms can explain the effects or discrepancies. Given the positive results, saffron presents itself as a promising supplement and adjunct therapy for managing CVD and its risk factors.
Abstract
INTRODUCTION Cardiovascular disease (CVD) is one of the leading causes of death and disability in the world and is estimated to involve more people in the next years. It is said that alternative remedies such as herbs can be used to manage the complications of this disease. For this reason, we aimed to conduct this meta-analysis to systematically assess and summarize the effects of saffron supplementation as an important herb on cardiovascular risk factors in adults. METHODS A systematic search was done in PubMed, Scopus, and Web of Science to find eligible articles up to September 2022. Randomized controlled trials (RCTs) that evaluated the effects of saffron on lipid profiles, glycemic control, blood pressure, anthropometric measures, and inflammatory markers were included. In the meta-analysis, 32 studies were taken into account (n = 1674). RESULTS Consumption of saffron significantly decreased triglyceride (TG) (WMD = -8.81 mg/dl, 95%CI: -14.33, -3.28; P = 0.002), total cholesterol (TC) (WMD = -6.87 mg/dl, 95%CI: -11.19, -2.56; P = 0.002), low density lipoprotein (LDL) (WMD = -6.71 mg/dl, 95%CI: -10.51, -2.91; P = 0.001), (P = 0.660), fasting blood glucose (FBG) level (WMD = -7.59 mg/dl, 95%CI: -11.88, -3.30; P = 0.001), HbA1c (WMD = -0.18%, 95%CI: -0.21, -0.07; P < 0.001), homeostasis model assessment-insulin resistance (HOMA-IR) (WMD = -0.49, 95%CI: -0.89, -0.09; P = 0.016), systolic blood pressure (SBP) (WMD = -3.42 mmHg, 95%CI: -5.80, -1.04; P = 0.005), tumor necrosis factor α (TNF-α) (WMD = -2.54 pg/ml, 95%CI: -4.43, -0.65; P = 0.008), waist circumference (WC) (WMD = -1.50 cm; 95%CI: -2.83, -0.18; P = 0.026), malondialdehyde (MDA) (WMD = -1.50 uM/L, 95%CI: -2.42, -0.57; P = 0.001), and alanine transferase (ALT) (WMD = -2.16 U/L, 95%CI: -4.10, -0.23; P = 0.028). Also, we observed that saffron had an increasing effect on total antioxidant capacity (TAC) (WMD = 0.07 mM/L, 95%CI: 0.01, 0.13; P = 0.032). There was linear regression between FBG and the duration of saffron intake. Additionally, the non-linear dose-response analysis has shown a significant association of saffron intervention with HDL (P = 0.049), HOMA-IR (P = 0.002), weight (P = 0.036), ALP (P = 0.016), FBG (P = 0.011), HbA1c (P = 0.002), and TNF-α (P = 0.042). A non-linear association between the length of the intervention and the level of HDL and DBP was also found. DISCUSSION That seems saffron could effectively improve TG, TC, LDL, FBG, HbA1c, HOMA-IR, SBP, CRP, TNF-α, WC, MDA, TAC, and ALT.
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The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.
Zamani, M, Zarei, M, Nikbaf-Shandiz, M, Hosseini, S, Shiraseb, F, Asbaghi, O
Frontiers in nutrition. 2022;9:1013055
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Despite advances in medicine, cardiovascular disease (CVD) still remains the primary cause of deaths worldwide. Many of the risk factors of CVD, such as elevated levels of blood fats, high blood pressure, abdominal obesity and poor blood sugar control, can be improved and managed by behaviour, lifestyle and dietary intervention as well as supplements. Berberine (BBR) is a plant-derived compound, available as a supplement, which has gained the attention of researchers due to its ability to modulate cardiovascular risk factors. This dose-response meta-analysis sought to generate a comprehensive overview of the effect of BBR on the risk factors for CVD in adults. The analysis included 49 randomised clinical trials. The results showed BBR significantly reduced blood fats such as total cholesterol, triglycerites and low-density lipoprotein (LDL). It also improved markers of blood sugar control such as fasting blood sugar levels, insulin, HbA1c, HOMA-IR and blood pressure and body weight, whilst enhancing high-density lipoprotein (HDL). The optimal dose of BBR was 1 g/day for triglycerides, total cholesterol, and weight loss. For insulin and HOMA-IR the best effects were seen with 1.8 g/day and for HDL 5 g/day. The most effective timeframe to impact fasting blood sugars seemed to be 40 weeks, and 50 weeks to influence blood pressure and waist circumference. In conclusion, BBR supplementation had beneficial effects on reducing risk factors for CVD, particularly in subgroups with impaired metabolic health. There was no substantial impact on liver enzymes (AST, ALT) or inflammatory markers (CRP, IL-6). Furthermore the supplement was largely ineffective in people with normal body mass index.
Abstract
UNLABELLED Cardiovascular disease (CVD) is a major concern today. Herbal medicine is one helping way to control CVD risks. One conclusive of herbal medicine is Berberine (BBR) and converse about it still exists, to clarify this issue, this meta-analysis was performed. PubMed/Medline, Scopus, and Web of Science were searched for RCTs in adults on the effect of BBR supplementation on CVD risk factors up to July 2022. The pooled results showed BBR significantly reduced triglyceride (WMD = -23.70 mg/dl; 95%CI -30.16, -17.25; P < 0.001), total cholesterol (WMD = -20.64 mg/dl; 95%CI -23.65, -17.63; P < 0.001), low-density lipoprotein WMD = -9.63 mg/dl; 95%CI, -13.87, -5.39; P < 0.001), fasting blood glucose (FBG) (WMD = -7.74 mg/dl; 95%CI -10.79, -4.70; P < 0.001), insulin (WMD = -3.27 mg/dl; 95%CI -4.46,-2.07; P < 0.001), HbA1c (WMD = -0.45%; 95%CI -0.68, -0.23; P < 0.001), HOMA-IR (WMD = -1.04; 95%CI -1.55, -0.52; P < 0.001), systolic blood pressure (WMD = -5.46 mmHg; 95%CI -8.17, -2.76; P < 0.001), weight (WMD = -0.84; 95%CI -1.34,-0.34; P < 0.001), body mass index (WMD = -0.25 kg/m2; 95%CI -0.46, -0.04; P = 0.020), while increased high-density lipoprotein (HDL) (WMD = 1.37 mg/dl; 95%CI 0.41,2.23; P = 0.005). The optimal dose of BBR was 1 g/day for TG, TC, and weight, 1.8 g/day for insulin and HOMA-IR, and 5 g/day for HDL. FBG's most efficient time frame was 40 weeks from the beginning of supplementation, whereas DBP and waist circumference was 50 weeks. In conclusion, the lipid profile, FBG balance, obesity parameters, and SBP were improved with BBR supplementation. SYSTEMATIC REVIEW REGISTRATION CRD42022347004.