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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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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:
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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Predictive metabolites for incident myocardial infarction: a two-step meta-analysis of individual patient data from six cohorts comprising 7897 individuals from the COnsortium of METabolomics Studies.
Nogal, A, Alkis, T, Lee, Y, Kifer, D, Hu, J, Murphy, RA, Huang, Z, Wang-Sattler, R, Kastenmüler, G, Linkohr, B, et al
Cardiovascular research. 2023;119(17):2743-2754
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Heart disease is a major cause of death worldwide. Individuals at risk are usually identified by the presence of diseases such as obesity and diabetes, and lifestyle factors such as smoking. However, there is a new understanding that when the body converts food into energy it creates by-products which might play an important role in the development of heart disease. Better understanding of these may be able to aid the identification of individuals at risk. This analysis of 7897 participants from 6 different cohort studies aimed to determine biomarkers associated with a heart attack. The results showed there were 56 metabolites associated with heart attack, some of which were associated with an increased occurrence and some a decreased occurrence. Most of the identified metabolites were lipids. Metabolites involved in bile acid production and amino acids were also identified. It was concluded that these metabolites may act as an indicator for individuals who are at risk of heart attack, however further research is needed. This study could be used by healthcare professionals to understand that the science behind the use of metabolites to indicate risk for heart attack is developing but still in its infancy.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There are certain lipids and amino acids that are associated with the incidence of MI, but the use of these to identify people at risk of MI is still in its infancy
- Current proven strategies to identify those at risk should take precedence over the measurement, identification and use of metabolites. However, this area of research is of current interest.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Individuals at risk of cardiovascular disease are usually identified by the presence of comorbidities (e.g. obesity and diabetes), and lifestyle factors (e.g. smoking). However, there is a new understanding that certain metabolites may be associated with myocardial infarction (MI) and a better understanding of these may be able to aid the identification of individuals at risk. This meta-analysis aimed to determine metabolites associated with a MI.
Methods
- This meta-analysis of 6 cohort studies from the USA and Europe involved 7897 participants
- The primary outcome was the metabolites associated with incident MI
- The secondary outcome was the metabolites associated with prevalent MI
- A total of 1442 metabolites were measured.
Results
- There were 1373 MI cases from the studies
- The results showed that there were 56 metabolites associated with MI, 42 had a direct association and 14 had an inverse relationship
- Most of the identified metabolites were lipids (n=21) and amino acids (n=17)
- Of the lipids, 3-methyladipate and 1-palmitoyl-2-linoleoyl-glycerol (16:0/18:2) were associated with a higher risk of MI (HR estimates ranged from 1.28; 95% confidence interval (CI) = 1.13–1.44, P < 0.001 to 1.21; 95% CI = 1.08–1.35, P = <0.005 respectively)
- Of the amino acids, 4-hydroxyphenylacetate and cystathionine had the largest increase in risk (HR estimates 1.24; 95% CI = 1.11–1.38, P = <0.01 and 1.2; 95% CI = 1.07–1.35, P = <0.01 respectively)
- When the meta-analysis was stratified by race, it showed that out of the 56 metabolites identified, the majority were associated with white individuals (n=41), whereas only 18 were associated with black individuals. Of these, 3 were specific to individuals with an African ancestry.
Conclusion
- It was concluded that certain metabolites and their associated pathways may help to identify individuals at risk for MI before disease onset and lead to better prevention
Clinical practice applications:
- Research into metabolite association with increased risk of MI is still in its infancy and has little merit until we understand the mechanisms involved and the direction of causation
- It does however give an idea of the tools that may be developed in the future that will aid identification and help to develop prevention strategies
- The metabolites associated with MI may be racially specific and further understanding is needed on this. Hence the data should be interpreted with caution.
Considerations for future research:
- Whilst associations are indicative of relationships, they do not identify causation. Future research should focus on the pathways which may link the metabolites with MI
- Identifying these pathways will also help to develop prevention strategies pertinent to specific nutrients
- A better understanding of how metabolites may be racially distinct is also required.
Abstract
AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies. METHODS AND RESULTS We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors and then performed a fixed effect inverse variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI. On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26-1.56], P < 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67-0.82), P < 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis. CONCLUSIONS In the most comprehensive metabolomic study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings.
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Effect of Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis.
Yuan, X, Wang, J, Yang, S, Gao, M, Cao, L, Li, X, Hong, D, Tian, S, Sun, C
International journal of endocrinology. 2022;2022:6999907
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The prevalence of obesity and metabolic syndrome may increase the risk of cardiovascular disease (CVD), diabetes, and neurological conditions. The imbalance in glucose and lipid metabolism and hypertension characterises the development of these chronic diseases. Intermittent fasting (IF) has been considered an effective dietary strategy for reducing the risk of obesity, insulin resistance, dyslipidaemia, diabetes, and CVD. This systematic review and meta-analysis include ten randomised controlled trials to evaluate the effects of IF intervention on glucose and lipid metabolism in people with metabolic syndrome. IF intervention regulated glucose metabolism by improving fasting blood glucose, glycosylated haemoglobin, insulin, and insulin resistance. IF intervention also positively impacted the body mass index and waist circumference. The total cholesterol, low-density lipoprotein levels, and triglyceride levels also improved, followed by the IF, showing the impact on lipid metabolism. Further robust studies are required due to heterogeneity between the included studies in type of IF, duration, the health status of participants, ethnicity, and outcome measurements. However, healthcare professionals can use the results of this systematic review and meta-analysis to understand the therapeutic effect of IF intervention on glycolipid metabolism in people with metabolic syndrome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IF does not require calorie restriction which may result in greater compliance
- IF does not restrict macronutrients such as CHO and fats, so may avoid the exclusion of key nutrients e.g. healthy fats and wholegrains.
- IF may have fewer adverse effects on daily routines and quality of life, which may mean adherence is easier.
- Improved glucose and lipid metabolism may prevent the development of chronic health conditions such as T2D, CVD and cancer.
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:
Management of glucose and lipid metabolism can be achieved through weight reduction using dietary interventions such as very low calorie or CHO diets, which may be effective but difficult to sustain long term. An alternative approach for weight management, improved insulin resistance and subsequent prevention of comorbitities e.g. Type 2 Diabetes (T2D), Cardiovascular Disease (CVD) and cancer, is Intermittent Fasting (IF). such as time restricted or periodic fasting.
This study summarises the effects of IF dietary interventions lasting less than three months in overweight and obese women with Metabolic Syndrome, defined as the presence of any metabolic dysfunction including obesity, hyperglycaemia, dyslipidaemia or hypertension.
The meta-anlaysis was carried out following PRISMA guidelines. A literature search in PubMed and Medline using the keywords obesity/overweight, IF diet, metabolic syndrome, RCT’s and humans resulted in 10 studies with 12 types of intervention for analysis. The following outcomes were evaluated: glucose and lipid metabolism, insulin resistance, weight loss and blood pressure.
Results were analysed in R software using mean differences and 95% confidence intervals, and either random or fixed effects depending on the Cochrane’s Q and I(2) statistics. Funnel plots were inspected for potential bias and Egger’s regression tests for publication bias.
There were significant differences before and after the interventions for all glucose and lipid metabolism markers as well as body weight and systolic blood pressure :
Glucose metabolism:
- Fasting glucose reduced by 0.15mmol/L
- Insulin plasma reduced by 13.25uUI
- HbA1c reduced by 0.08%
- HOMA-IR (insulin resistance index) reduced by 0.31 on average
Lipid metabolism:
- Total cholesterol reduced by 0.32mmol/L
- LDL reduced by 0.22mmol/L
- Triglyceride reduced by 0.04mmol/L
Weight loss:
- Body weight reduced by 1.87kg
- BMI reduced by 0.8kg/m2
- Waist circumference reduced by 2.08cm
Blood pressure:
- Systolic reduced by 2.58mmHg
- Diastolic reduced by 3.12mmHg
Despite limitations of the meta-analysis, this study demonstrates IF has therapeutic effects on those with disordered lipid and glucose metabolism, and may prove to be an effective and sustainable approach.
Clinical practice applications:
- IF may be an effective alternative to restricted calorie or CHO diets for weight management with the associated benefits of glucose and lipid metabolism.
- IF has been shown to have therapeutic effects on individuals with impaired glucose and lipid metabolism.
- IF may be considered as a sustainable lifestyle choice rather than a ‘weight loss’ programme such as a very low calorie diet, which can result in poor quality of life and subsequent reduced adherence.
- Since it may take time for impaired glucose and lipid metabolism to progress to more serious disease states, establishing IF as an early intervention, may be considered as a prudent form of preventative medicine.
- IF has shown to have other health benefits such as reduced blood pressure and may be considered as adjuvant therapy.
Considerations for future research:
- Compares the effects of IF on different ethnicities, sex and age categories
- Evaluates the effect of IF on other disease states e.g. cancer, auto-immune conditions
- Assesses the response of other biomarkers e.g. inflammatory cytokines
- Compares different types and durations of IF on health biomarkers (eg periodic, time restricted)
Abstract
The question of whether or not intermittent fasting diets improve the clinical indicators of glycolipid metabolism remains unclear. This study systematically reviewed the relevant clinical trials to evaluate the effects of intermittent fasting diet on glucose and lipid metabolism and insulin sensitivity in patients with metabolic syndrome. To evaluate the effect of intermittent fasting diet intervention on patients with disorders of glucose and lipid metabolism, random-effect or fixed-effect meta-analysis models were used to calculate the average difference before and after intermittent fasting diet intervention and the corresponding 95% confidence intervals (CIs). After intermittent fasting diet intervention, in terms of glucose metabolism, fasting blood glucose reduced by 0.15 mmol/L (95% CI: -0.23; -0.06), glycosylated hemoglobin reduced by 0.08 (95% CIs: -0.25; -0.10), insulin plasma levels reduced by 13.25 uUI (95% CIs: -16.69; -9.82), and HOMA-IR decreased by 0.31 on an average (95% CIs: -0.44; -0.19). In addition, BMI decreased by 0.8 kg/m2 (95% CIs: -1.32; -0.28), body weight reduced by 1.87 kg (95% CIs: -2.67; -1.07), and the waist circumference decreased by 2.08 cm (95% CIs: -3.06; -1.10). Analysis of lipid metabolism showed that intermittent fasting diet intervention effectively reduced the total cholesterol level by 0.32 mmol/L (95% CIs: -0.60; -0.05), low-density lipoprotein level by 0.22 mmol/L (95% CIs: -0.37; -0.07), and triglyceride level by 0.04 mmol/L (95% CIs: -0.15; -0.07). Intermittent fasting diets have certain therapeutic effects on blood glucose and lipids in patients with metabolic syndrome and significantly improve insulin resistance. It may be considered as an auxiliary treatment to prevent the occurrence and development of chronic diseases.
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4.
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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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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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:
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.
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5.
Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis.
Liang, T, Xie, X, Wu, L, Li, L, Yang, L, Gao, H, Deng, Z, Zhang, X, Chen, X, Zhang, J, et al
Frontiers in nutrition. 2022;9:825897
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Type 2 diabetes (T2D) is a serious medical condition often requiring antidiabetic drug management. Although commonly used antidiabetic drugs effectively control glucose levels, their tolerability profiles differ, causing various side effects. Probiotics can be used as single or multi strains to reduce glycaemic and lipid indicators and avoid the negative effects of antidiabetic medications. The study included twenty-five randomised controlled trials, of which fourteen studies assessed the effectiveness of probiotics (single probiotics, multi-strain probiotics, and probiotics with co-supplements), and eleven studies included different antidiabetic drugs such as Thiazolidinedione (TZD), Glucagon-like peptide-1 receptor agonists (GLP-1 RA), Dipeptidyl peptidase IV inhibitors (DPP-4i), and Sodium-glucose co-transporter 2 inhibitors (SGLT-2i). This systematic review and meta-analysis compared the effectiveness of probiotic and antidiabetic drugs on glycaemia, lipid profile and blood pressure in T2D patients. Probiotics were less effective than specific antidiabetic drugs in reducing fasting blood sugar levels (FBS), HbA1c levels, and triglycerides. Different probiotic formulations were effective in reducing the HOMA-IR index, total cholesterol (TC), triglycerides (TG), and systolic and diastolic pressure (SBP and DBP). A subgroup analysis showed a greater reduction in FBS, HbA1c, TC, TG, and SBP in obese and elderly participants, those who participated for a longer duration, and those from Eastern origins. Considering the high heterogeneity in baseline study characteristics among the studies included in this systematic review and meta-analysis, further studies are required to evaluate the effects of probiotics and antidiabetic drugs. However, healthcare professionals can use the study to understand the effect of probiotics and antidiabetic drugs in reducing glycaemic, lipid and hypertension profiles.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Glucose-lowering drugs, except for DPP-4i, reduced FBS and HbA1c more than probiotics; and SGLT-2i induced the greatest decrease in HbA1c
- A BMI ≥ 30 kg/m2 showed a significant decrease in FBS and the HOMA-IR index compared with those with lower BMI
- Weight loss induced by glucose-lowering drugs and probiotic supplementation plays an important role in glycaemic control in obese patients with type 2 diabetes.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This meta-analysis compared the effects of probiotics and glucose-lowering drugs thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) on various outcome measures in patients with type 2 diabetes (T2D).
Methods
A search was performed on PubMed, Web of science, Embase, and Cochrane Library between January 2015 - April 2021.
Results
25 randomised controlled trials (RCT) were included (2843 participants). 14 RCTs (842 participants) involved the administration of single probiotics, multi-strain probiotics, and probiotics with co-supplements, and 11 RCTs (2001 participants) involved TZD, GLP-1 RA, SGLT-2i, and DPP-4i. Participants in 7 of the studies had T2D, aged ≤ 55 years old. 8 RCTs included participants with a mean BMI ≥ 30 kg/m2, and 11 RCTs participants had a mean BMI < 30 kg/m2.
Effects of probiotics:
- Fasting Blood Sugar (FBS): A reduction (−1.42, −0.32 mg/dL, p=0.000)
- Glycated hemaglobin (HbA1c): No reduction (p = 0.000)
- Insulin Resistance (HOMA-IR): A decrease (−0.64, −0.31; p = 0.780), regardless of probiotic strain or with a co-supplement
- Insulin: Not significant (p = 0.000). Subgroup analysis: no reduction
- Total Cholesterol (TC): No difference (p = 0.941). Subgroup analysis: reduction from multi-species probiotics (−0.36, −0.01 mg/dL, p = 0.871)
- Triglycerides: Difference (−0.25 mg/dL, p = 0.958)
- LDL-C: No changes (p = 0.189)
- HDL-C: No increase (p = 0.014)
- Systolic Blood Pressure (SBP): A decrease (−6.44, −0.08 mmHg, p = 0.044)
- Diastolic Blood Pressure (DBP): A reduction (−4.53, −0.80 mmHg, p = 0.206).
Effects of glucose-lowering drugs:
- FBS: A decrease (−4.22 mg/dL, −1.24 mg/dL, p = 0.000)
- HbA1c: A decrease (−2.51%, −0.52%, p = 0.000) with TZD, GLP-1 RA, SGLT-2i, and DPP- 4i; a reduction with SGLT-2i (p = 0.003)
- TC: No difference (p = 0.000). Subgroup: no decrease with single species probiotics and probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i)
- TG: No difference (p = 0.000)
- . HDL-C: No increase (p = 0.000). Subgroup: a decrease with TZDs (−2.37, −0.72 mg/dL). No difference with probiotic strains, or probiotics with co-supplements, GLP-1 RA, and DPP-4i
- LDL-C: No changes (p = 0.000), Subgroups: no difference with probiotic strains, probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i).
Limitations
Limited number of studies for TZD and SGLT-2i, making results potentially unreliable.
Conclusions
Multi species probiotics are worth considering as an adjunct to glucose-lowering drugs, and for improving lipid profiles and hypertension.
Clinical practice applications:
- Probiotic supplementation reduced the HOMA-IR index
- Multi-species probiotics were associated with reduction in TC and TG levels
- DPP-4i only decreased TG levels
- TZD was associated with decrease in HDL-C, whereas probiotic supplementation was associated with higher decrease in SBP and DBP and that GLP-1 RA increases the risk of hypoglycaemia.
Considerations for future research:
- Semaglutide was associated with an increased risk for hypoglycaemia compared with a placebo, indicating that the safety of semaglutide needs further study
- Dietary and physical activity should be considered in future studies
- Heterogeneity in some indicators may be due to differences in study baseline characteristics,Larger trials needed to support the results of this meta-analysis.
Abstract
The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension.
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6.
Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Plain language summary
Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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7.
The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Tian, J, Feng, B, Tian, Z
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:8278744
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Plain language summary
Dyslipidaemia is a common comorbidity of type 2 diabetes mellitus (T2DM), which is characterised by elevated triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) level, and/or decreased high-density lipoprotein cholesterol (HDL-c) concentrate serum. Dyslipidaemia and dysglycemia interact with each other, and they are the main risk factors of macro- and microvascular diseases in T2DM. The aim of this study was to outline curcumin’s efficacy and possible uses in clinical practice. This study is a meta-analysis of nine randomised controlled trials (RCTs). A total of 604 participants (284 in the curcumin group and 281 in the control group) were included in the selected studies. The design of all trials was parallel; seven of them were double-blind RCTs, and the other two were open label RCTs. Results show that curcumin significantly decreased TG, TC, fasting blood glucose, and haemoglobin A1C levels and also led to a reduction in LDL-c and an elevation in HDL-c concentration, although with no statistical difference. Authors conclude that curcumin has promising effects on the lipid profile and glycaemic status in patients with T2DM. It indicated that curcumin might be a favourable therapeutic option for T2DM patients with mixed dyslipidaemia.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dyslipidemia and dysglycemia interact with each other, and are risk factors of macro- and microvascular diseases in T2DM.
Although effective intervention strategies exist for improving glycemic status of T2DM patients, they often need lipid-lowering drugs simultaneously to prevent CVD.
- Novel therapeutic interventions are needed to manage dyslipidemia and dysglycemia in diabetic patients, when statin therapy to treat dyslipidemia, may increase the risk of new-onset diabetes and myopathy.
- Other clinical studies have highlighted the benefits of curcumin supplementation on lipid profile and glycemic status. Clarifying its effects is important for assessing its potential as an alternative and complementary medicine on improving the metabolic status of T2DM patients.
- Overall there is limited evidence and further research is required.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This meta-analysis aimed to evaluate the effects of curcumin on lipid profile in patients with type 2 diabetes mellitus (T2DM), including: serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), and/or high-density lipoprotein cholesterol (HDL-c). Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were also assessed.
Methods
A search was performed on Pubmed, Embase, Web of Sciences, and the Cochrane Library up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies were included in the review, with a total of 604 participants (284 in the curcumin group and 281 in the control group) of mean age from 41 to 60.95 years. Curcumin forms varied among the studies including, turmeric, curcuminoids, and curcumin. The dosage of curcumin in the intervention group ranged from 80 to 2100 mg/day. The duration of intervention was between 4 weeks and 3 months in different studies.
- Effect of Curcumin on TG: A difference was observed between curcumin supplementation and control (p = 0.03), indicating curcumin could reduce serum TG.
- Effect of Curcumin on TC: The mean difference in net changes of TC between intervention and control groups was −8.91mg/dL (p = 0.001), suggesting that curcumin could decrease serum TC.
- Effect of Curcumin on LDL-C: No difference in the net change of LDL-c between intervention and control groups (p = 0.26).
- Effect of Curcumin on HDL-C: No difference in HDL-c between intervention and control groups (p = 0.56).
- Effect of Curcumin on FBG: Curcumin reduced blood glucose levels compared with control treatment (p = 0.002). The effect was greater in trials with the treatment duration >8w (p = 0.037), curcumin dose >100mg/day (p = 0.004), and with the participants receiving the other therapy (p = 0.002).
- Effect of Curcumin on HbA1c: HbA1c (%) decreased in the intervention group compared with the control group (p ≤ 0.001).
Conclusion
Curcumin has promising effects on the lipid profile and glycemic status of T2DM patients and might be a therapeutic option for T2DM patients with mixed dyslipidemia.
Clinical practice applications:
- Limitations were the small number of included studies, mostly with small sample sizes. In some studies, treatment duration was short (<2 months) and may be insufficient to see a difference in some metabolic parameters.
- The reduction of FBG and HbA1c after treatment with curcumin suggested that it improved the glycemic metabolism in the T2DM patients studied.
- Studies have shown that curcumin could promote insulin release through inducing β-cell electrical activity and lower serum glucose level via decreasing the production of hepatic glucose and increasing glucose uptake. While changes of LDL-c and HDL-c was not statistically significant, the authors note the effect of curcumin on LDL-c/HDL-c and its potential clinical significance could not be neglected.
- The reduction of dyslipidemia by curcumin supplementation could improve the glucose metabolic status of T2DM patients, and multiple molecular targets including PPAR-c, cholesteryl ester transfer protein, and lipoprotein lipase contribute to the beneficial effects of curcumin.
Considerations for future research:
- While significant heterogeneity was found in pooled analyses of TG, LDL-c, FBG, and Hb1Ac, a random-effects model revealed that trial duration, curcumin dosage, and other therapy may contribute to the variation in pooled effects, and these aspects could be discussed in future studies.
- The study found that a higher dose of curcumin was more powerful in reducing plasma TG and FBG concentrations, but further large-scale multicenter RCTs are required to confirm the clinical improvement of curcumin.
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mg/dL (95% CI: -36.47 to -1.47; P=0.03) for triglyceride (TG), -8.91 mg/dL (95% CI: -14.18 to -3.63, P=0.001) for total cholesterol (TC), -4.01 mg/dL (95% CI: -10.96 to 2.95, P=0.259) for low density lipoprotein cholesterol (LDL-c), 0.32 mg/dL (95% CI: -0.74 to 1.37, P=0.557) for high density lipoprotein cholesterol (HDL-c), -8.85 mg/dL (95% CI: -14.4 to -3.29, P=0.002) for fasting blood glucose (FBG), -0.54 (95% CI: -0.81 to -0.27, P ≤ 0.001) for glycated hemoglobin (HbA1c) (%) compared with controls. There was a significant heterogeneity for the influence of curcumin on TG, LDL-c, FBG and HbA1c. Subgroup analysis revealed that the heterogeneity mainly attributed to trial period, curcumin dosage and other therapy. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with T2DM. Further studies with large-scale are still needed to confirm the results.
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8.
Lipid Intake and Breast Cancer Risk: Is There a Link? A New Focus and Meta-Analysis.
Lodi, M, Kiehl, A, Qu, FL, Gabriele, V, Tomasetto, C, Mathelin, C
European journal of breast health. 2022;18(2):108-126
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Incidence of breast cancer is the leading cause of cancer-related mortality, accounting for 15.5% of all cancer-related deaths. However, there is a lack of complete understanding of the effects of different types of dietary lipids on breast cancer development, such as saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), dietary cholesterol, polyunsaturated fatty acids (PUFA), and unsaturated trans fatty acids (TFA). An evaluation of the effect of lipid consumption on breast cancer and the impact it has on menopausal status was conducted in this meta-analysis, which included forty-four studies. Increased saturated fatty acid intake was associated with an increased risk of breast cancer in postmenopausal women. However, breast cancer risk was not associated with increased consumption of total fat, SFA, MUFA, PUFA, and cholesterol in premenopausal women. The effects of estrogen and the release of proinflammatory cytokines by adipocytes should be evaluated, as well as other pathways that contribute to the development of breast cancer. There is a need for further robust studies to evaluate the effects of different types of lipid consumption on breast cancer. Although the association between SFA and breast cancer is weak, healthcare professionals can use this study's findings to better understand the detrimental effect of SFA, despite the fact that there is a great deal of heterogeneity in the current analysis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
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:
- Among lifestyle-related breast cancer risk factors, the role of diet in breast cancer remains uncertain.
- The authors highlight a weak association between high SFA consumption and breast cancer risk in post-menopausal women.
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
Objectives
- To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk.
Results
- Forty-four articles were included in the meta-analysis, consisting of 28 case-control studies and 16 cohort studies.
- In total, this meta-analysis involved 1,185,896 women, of whom 54,553 had breast cancer.
- There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women.
- In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03–1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85–1.19; p = 0.93).
Limitations
- Studies included in the meta-analysis were carried out on populations from five continents with significant cultural and dietary diversity, and well as different types of oils used in the diet
Conclusion
- At this stage, the authors state it is not possible to establish nutritional recommendations regarding the consumption of lipids to decrease breast cancer risk.
Clinical practice applications:
- The results of this meta-analysis does not demonstrate a statistically significant link between high consumption of total lipids, PUFA, MUFA and cholesterol and the occurrence of breast cancer.
- However, the results suggest that there is an association between SFA intake and breast cancer risk in postmenopausal women, although this was only found in case-controlled studies and not cohort studies.
- While obesity is a known breast cancer risk factor after menopause, the link between the effect of diet and the effect of obesity on the breast may be through different mechanisms.
- The authors investigated if high lipid consumption acts on breast tissue by the same mechanisms as obesity, and found the association between SFA intake and breast cancer risk in postmenopausal women must be through other biological explanations.
- The authors found that while high SFA consumption may increase breast cancer risk among post-menopausal women, biological mechanisms linking SFA and breast cancerogenesis are still unknown.
- The meta-analysis found high blood cholesterol levels appear to increase the risk of breast cancer. However, the authors could not confirm that high dietary cholesterol intake is a risk factor for breast cancer. The authors postulated this may be in part due to the low proportion of cholesterol (about 30%) in the diet, while the rest comes from the degradation of lipids and carbohydrates by the liver.
Considerations for future research:
- As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption
Abstract
Objective: To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk. Materials and Methods: We conducted a systematic review of the literature and a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all cohort and case-control studies published up to December 2020 with subgroup analysis according to menopausal status. Results: We included 44 articles for analysis. There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women. In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03-1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85-1.19; p = 0.93). Conclusion: There was a weak association between high SFA consumption and breast cancer risk in post-menopausal women, however there was high heterogeneity for this analysis. As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption.
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9.
Effect of 12-Week Daily Intake of the High-Lycopene Tomato (Solanum Lycopersicum), A Variety Named "PR-7", on Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Nishimura, M, Tominaga, N, Ishikawa-Takano, Y, Maeda-Yamamoto, M, Nishihira, J
Nutrients. 2019;11(5)
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Tomatoes are a rich source of lycopene, a compound believed to have many health benefits. Researchers in Japan conducted a randomised, double-blind, placebo-controlled trial to investigate the effects of eating a type of tomato bred to be high in lycopene on 74 healthy volunteers with raised cholesterol levels. Participants were given 50g per day of either semi-dried high-lycopene tomato or lycopene-free tomato. Those eating the high-lycopene tomatoes significantly reduced their levels of LDL cholesterol over 12 weeks. The researchers concluded that their findings support the health benefits of eating tomatoes rich in lycopene.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Lycopene, a carotenoid, has antioxidant effects and exhibits the highest physical quenching rate constant for singlet oxygen.
- Lycopene has also been reported to inhibit the production of serum lipid peroxide and oxidize low-density lipoprotein (LDL)
- This study reported that the intake of 50g of high-lycopene (lycopene, 22.0-27.8mg) for 12 weeks significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL.
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:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group study was conducted to investigate the effects of the regular and continuous intake of high-lycopene tomato, a variety named PR-7, for 12 weeks on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels > 120 to <160mg/dL.
The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50g of semi-dried PR-7 (lycopene, 22.0-27.8mg) per day. Medical interviews were conducted, vital signs were monitored, and blood and saliva samples were taken at 0 (baseline) and at 4, 8 and 12 weeks.
Primary clinical outcomes were:
- The intake of high-lycopene tomato improved LDL-C at week 12 when compared to the placebo group (Week 12: placebo, 4,1 +- 15.7mg/dL; high-lycopene tomato, -3.7 +- 13.8.mg/dL; p=0.027).
- Based on a subgroup analysis, the ingestion of high-lycopene tomato significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL at week 12 (Week 12: placebo, 4.3 15.1 mg/dL; high-lycopene tomato, +- 5.1 9.5 mg/dL; p = 0.030).
Secondary clinical outcomes were:
- There were no significant differences between the high-lycopene tomato and placebo groups in terms of lipid profiles comprising of total cholesterol (TC), HDL-C, triglycerides (TG), LDL-C/HDL-C ratio, and non-HDL, and adiponectin.
- The intake of high-lycopene tomato increased lycopene levels compared to the placebo group (Week 12: placebo,
+-24.2 49.3 g/dL; high-lycopene tomato, 22.7 47.9 g/dL; p < 0.001).
- In addition, beta-carotene levels increased in the high-lycopene tomato group compared to those in the placebo group at week 12 (Week 12: placebo, 0.9 13.6 g/dL; high-lycopene tomato, 12.0 24.5 g/dL; p = 0.009).
Clinical practice applications:
- A previous meta-analysis demonstrated that LDL-C decreases when more than 25 mg per day of lycopene is ingested. The biological mechanism was associated with a reduction in 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity in the liver, activation of LDL-receptors, and increased expression of the ABCA1 transporter gene, the key component of HDL-C production.
- This study also suggests that there is a decrease in LDL-C at 12 weeks in subjects with LDL-C ranging from 120–139 mg/dL.
- Based on these findings, a practitioner could therefore consider recommending 25mg of lycopene to help reduce LDL-C in patients with an LDL-C range of 120–139 mg/dL for at least 12 weeks.
Considerations for future research:
- Lycopene has been reported to possess the strongest singlet oxygen scavenging ability among the eight carotenoids, as measured by the singlet oxygen absorption capacity method, and some researchers have found that lycopene and tomato display antioxidant effects. However, other reports suggest that ingesting lycopene does not affect oxidative markers. These findings suggest that further investigation is needed to evaluate the effect of lycopene on oxidative markers.
- The LOX index is a biomarker for the early risk of arteriosclerosis, cerebral infarction, and myocardial infarction. Lycopene might be ineffective against LOX-1 which is a product of the peroxidation reaction. Additional studies with a longer intake period are required to investigate the effect of lycopene on the risk of arteriosclerosis.
- The subjects in this study were asked to avoid cooking the test food (semi-dried tomato). It is, therefore, necessary to investigate the differences in the effect of the high-lycopene tomato based on various cooking methods.
Abstract
Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to <160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0-27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p < 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe.