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1.
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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Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
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Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
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3.
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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4.
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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5.
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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6.
Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
Evidence Category:
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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:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
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7.
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.