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The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.
Santo André, HC, Esteves, GP, Barreto, GHC, Longhini, F, Dolan, E, Benatti, FB
Advances in nutrition (Bethesda, Md.). 2023;14(1):115-127
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Omega 3 polyunsaturated fatty acids (n-3PUFA) are long-chain polyunsaturated fatty acids essential to human health. They play a role in cell membrane integrity, immune and inflammation regulation, cognition and neuromuscular function. As the human body cannot make these fatty acids, they need to be obtained through diet or supplementation. Regarding skeletal muscle, recent research showed that n-3PUFAs may increase the uptake of amino acids by increasing the membrane fluidity in the muscle, and by activating pathways that inhibit protein breakdown. This led to the hypothesis that n-3PUFAs may enhance muscle mass gain and strength. This systematic review sought to gather all available evidence about the impact of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. The review included 14 studies with a total of 1443 participants. The authors found that n-3PUFA supplementation had no significant effect on muscle mass or muscle function in healthy young and older adults, however, a very small but significant positive effect was noted regarding muscle strength. In the discussion section, the authors explain the challenges of their review and how these findings integrate with the current understanding and other research findings. They concluded more research is needed to get a better insight into the effects of n-3PUFA on muscle function and the variants.
Abstract
The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.
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The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis.
Fairbairn, P, Dyall, SC, Tsofliou, F
The British journal of nutrition. 2023;129(3):428-441
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Due to the insidious onset, cognitive impairment often goes unnoticed for several years, with clinical diagnosis being made late into the disease progression. Cognition is critical for functional independence as people age, and intact cognition is vital for humans to communicate effectively. The aims of this study were to (i) investigate whether supplementation with a combination of omega-3 polyunsaturated fatty acids (n-3 PUFA) and B vitamins alone or as part of a multi-nutrient formula can prevent cognitive decline in older adults, and (ii) determine whether the effects of a single nutrient intervention with either n-3 PUFA or B vitamins could be modified by the status of the other nutrient. This study is a systematic review and meta-analysis of fourteen studies of which eleven were randomised controlled trials and the rest were post hoc analysis of randomised controlled trials. Results show a benefit of supplementing with nutrient formulas that contain both n-3 PUFA and B vitamins on global cognition and episodic memory with small to moderate effect sizes. In fact, they can help preserve cognition in the older adults. Authors conclude that more experimental work providing a combination of nutrients including both n-3 PUFA and B vitamins, in healthy older adults or those showing early signs of cognitive decline, is clearly warranted to better explore how nutrition can impact the trajectory of cognition in older adults.
Abstract
There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60-70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.
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The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Alshahrani, SM, Mashat, RM, Almutairi, D, Mathkour, A, Alqahtani, SS, Alasmari, A, Alzahrani, AH, Ayed, R, Asiri, MY, Elsherif, A, et al
Nutrients. 2022;14(21)
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The prevalence of cardiovascular disease increases as the modifiable risk factors increase, such as metabolic syndrome, obesity, type 2 diabetes, dyslipidaemia, and high blood pressure. Walnuts are a rich source of anti-inflammatory polyunsaturated fatty acids and omega-3 fatty acids. Walnuts are also known for their antioxidant properties and have been found to improve dyslipidaemia by reducing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). This systematic review and meta-analysis of thirteen randomised controlled trials evaluated the effects of walnut intake on lipid profile. Most of the included studies used walnut dosage ranging from 15 g to 99 g/day for six to sixteen weeks of intervention. The results of this systematic review and meta-analysis showed significant improvements in TC, LDL-c, and triglyceride (TG) levels. Subgroup analysis revealed greater improvement in TC, LDL-c, and TG in overweight and other comorbidities but had normal levels of TC and LDL-C. Additionally, female participants showed greater improvements in TG levels, followed by the walnut intervention. Intervention duration also affected the beneficial effect of the walnut intervention. Further robust studies are required to determine the effects of walnut intake on cardiovascular disease risk reduction due to the high heterogeneity between the included studies. However, healthcare professionals can use the results of this research to understand the benefits of including walnuts as part of a healthy diet and their impact on reducing dyslipidaemia.
Abstract
Cardiovascular diseases (CVD) are the leading causes of death worldwide. Dyslipidemia is a cardiometabolic risk factor of CVD, yet it can be modifiable. Walnuts have been suggested as a dietary intervention to improve the lipid profile. Therefore, we reviewed the literature to assess the evidence linking walnut intake to the improvement of blood lipids, including total cholesterol (TC), low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein (HDL-C) cholesterol, and triglycerides (TG). PubMed and Embase databases were searched from 2010 up to March 2022. We limited our search to randomized controlled trials conducted on humans and published in English during the specified period. Cochrane's risk of bias tool for interventional studies was used. A random-effects model was used for the meta-analysis, and weighted mean differences were obtained (WMD) Thirteen trials from the U.S., Europe, and Asia were included. Walnut intake was associated with significant reductions in TC (WMD: -8.58 mg/dL), LDL-C (WMD: -5.68 mg/dL), and TG (WMD: -10.94 mg/dL). Walnut consumption was not associated with HDL-C. Subgroup analysis showed that overweight/obese and those with comorbidities had more lipid improvement. A longer trial duration did result in further improvements. However, our results may be prone to bias due to extraneous confounding factors. Additionally, levels of heterogeneity were considerable for some outcomes of interest. Results from this meta-analysis provide evidence for the health benefits of walnuts on blood lipids. Walnuts possibly reduce the risk of CVD; thus, they can be successfully added to a dietary pattern to enhance health benefits.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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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.
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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Impact of Replacement of Individual Dietary SFAs on Circulating Lipids and Other Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials in Humans.
Sellem, L, Flourakis, M, Jackson, KG, Joris, PJ, Lumley, J, Lohner, S, Mensink, RP, Soedamah-Muthu, SS, Lovegrove, JA
Advances in nutrition (Bethesda, Md.). 2022;13(4):1200-1225
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Cardiovascular disease is one of the leading causes of mortality worldwide, and metabolic disorders such as diabetes, hyperlipidaemia, and hypertension contribute to this risk. Cardiometabolic disease (CMD) can be reduced by reducing saturated fatty acids (SFAs) and replacing them with unsaturated fatty acids (UFAs). Dietary SFA's are classified as a whole group in general dietary guidelines. However, blood lipid levels and other biomarkers of CMD may be affected differently by individual dietary SFAs. In this systematic review and meta-analysis, 44 randomised controlled trials were included that investigated the effects of replacing SFAs with individual dietary SFAs or UFAs on markers of CMD. CMD markers like Total cholesterol (TC), LDL cholesterol, and apoB concentrations were significantly reduced by replacing 1.5%TE of palmitic acid with oleic acid or UFAs for 14 days. The research also showed associations between apoB and LDL-cholesterol and apoA-I and HDL-cholesterol concentrations. Dietary palmitic acid substituted with UFAs significantly reduced fasting LDL-cholesterol and total cholesterol. The majority of studies included in this study focused on dietary palmitic acid and not much on stearic acid, myristic acid, or lauric acid. Therefore, further robust studies are required to assess the effect of individual dietary SFAs on the markers of CMD, including markers of inflammation, hemostasis, glycemic control, or metabolic hormones. Healthcare professionals can use this study to understand the benefits of substituting SFAs with UFAs on CMD markers.
Abstract
Little is known of the impact of individual SFAs and their isoenergetic substitution with other SFAs or unsaturated fatty acids (UFAs) on the prevention of cardiometabolic disease (CMD). This systematic literature review assessed the impact of such dietary substitutions on a range of fasting CMD risk markers, including lipid profile, markers of glycemic control and inflammation, and metabolic hormone concentrations. Eligible randomized controlled trials (RCTs) investigated the effect of isoenergetic replacements of individual dietary SFAs for ≥14 d on ≥1 CMD risk markers in humans. Searches of the PubMed, Embase, Scopus, and Cochrane CENTRAL databases on 14 February, 2021 identified 44 RCTs conducted in participants with a mean ± SD age of 39.9 ± 15.2 y. Studies' risk of bias was assessed using the Cochrane Risk of Bias tool 2.0 for RCTs. Random-effect meta-analyses assessed the effect of ≥3 similar dietary substitutions on the same CMD risk marker. Other dietary interventions were described in qualitative syntheses. We observed reductions in LDL-cholesterol concentrations after the replacement of palmitic acid (16:0) with UFAs (-0.36 mmol/L; 95% CI: -0.50, -0.21 mmol/L; I2 = 96.0%, n = 18 RCTs) or oleic acid (18:1n-9) (-0.16 mmol/L; 95% CI: -0.28, -0.03 mmol/L; I2 = 89.6%, n = 9 RCTs), with a similar impact on total cholesterol and apoB concentrations. No effects on other CMD risk markers, including HDL-cholesterol, triacylglycerol, glucose, insulin, or C-reactive protein concentrations, were evident. Similarly, we found no evidence of a benefit from replacing dietary stearic acid (18:0) with UFAs on CMD risk markers (n = 4 RCTs). In conclusion, the impact of replacing dietary palmitic acid with UFAs on lipid biomarkers is aligned with current public health recommendations. However, owing to the high heterogeneity and limited studies, relations between all individual SFAs and biomarkers of cardiometabolic health need further confirmation from RCTs. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020084241.
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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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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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Effect of Flaxseed (Linum usitatissimum L.) Supplementation on Vascular Endothelial Cell Morphology and Function in Patients with Dyslipidaemia-A Preliminary Observation.
Kanikowska, D, Malińska, A, Mickiewicz, A, Zawada, A, Rutkowski, R, Pawlaczyk, K, Sato, M, Bręborowicz, A, Witowski, J, Korybalska, K
Nutrients. 2022;14(14)
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Flaxseed appears to be a valuable source of polyunsaturated fatty acids, phytosterols and fibre, which lower lipids and have anti-atherogenic activity. The aim of this study was to determine the effects of 10 weeks of supplementation with the flaxseed (28g/day) on endothelial cells function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. This study is a prospective study of two groups of patients. The first group (n=14) was composed of lean (n=6), and obese (n=8) outpatients receiving therapy of lipoprotein apheresis (once every two weeks) for severe hyperlipidaemia. The second group was composed of 11 obese outpatients with dyslipidaemia receiving a diet at home. In both groups, flaxseed was given blindly. Results show that patients diagnosed with dyslipidaemia who took 28g daily of flaxseed showed a significant reduction in serum lipids but exhibited a slight beneficial effect on endothelial cells. However, it only shows that flaxseed might have the potential ability to improve endothelial function but, in obese patients, it does not have the potency to reverse endothelial ultrastructural changes observed in electron microscopy. Authors conclude that flaxseed supplementation produced consistent lipid-lowering effects and can modulate VEGF (endothelial cell marker) concentration depending on the severity of dyslipidaemia.
Abstract
CONTEXT Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. OBJECTIVE This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. MATERIALS AND METHODS Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. RESULTS Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. CONCLUSIONS Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.
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Blood levels of circulating methionine components in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.
Zhao, Y, Dong, X, Chen, B, Zhang, Y, Meng, S, Guo, F, Guo, X, Zhu, J, Wang, H, Cui, H, et al
Frontiers in aging neuroscience. 2022;14:934070
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Alzheimer’s disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss and cognitive deficits. Mild cognitive impairment (MCI) is a prodromal form of AD that is characterised by neurocognitive dysfunction. However, pathological changes associated with AD begin to occur in the brain at least 10 years before the onset of overt symptoms and clinical manifestations, making the discovery of early diagnostic methods and timely interventions important for AD management. The aim of this study was to determine the relationship between circulating methionine (Met) components and AD/MCI. This study is a systematic review and meta-analysis of thirty studies (10 case– control studies, 10 cohort studies, and 10 cross-sectional studies). Results show that: - individuals with AD compared with controls had significantly increased levels of homocysteine. - for people with MCI, there was no significant difference in blood homocysteine levels in the control group. - there were no differences in blood vitamin B12 levels between patients with AD or MCI and controls. Authors conclude that circulating Met components affect patients with AD compared to cognitively normal individuals, with patients exhibiting higher blood homocysteine levels. Additionally, high Met and S-adenosylmethionine levels are risk factors for AD, which supports the association between Met cycle components and AD/MCI.
Abstract
BACKGROUND Circulating methionine components have been reported to be associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI), although outcomes are not always consistent. MATERIALS AND METHODS Database searching was conducted using PubMed, Embase, Cochrane Library, and Web of Science from inception to 26 December 2021. In this study, two reviewers independently identified eligible articles and extracted the data. We used Joanna Briggs Institute (JBI) Critical Appraisal tools to assess the overall quality of the included studies. STATA software was employed to perform meta-analysis evaluating the standardized mean difference (SMD) with its 95% confidence intervals (CIs) using random-effects models. Evidence quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS Totally, 30 observational studies were eligible for inclusion. Compared with cognitively normal controls, patients with AD had increased homocysteine (Hcy) levels in the blood [standardized mean difference (SMD) = 0.59, 95% confidence interval [CI]: 0.36-0.82, P = 0.000], plasma (SMD = 0.39, 95% CI: 0.23-0.55, P = 0.000), and serum (SMD = 1.56, 95% CI: 0.59-2.95, P = 0.002). Patients with MCI were not significantly different from controls (SMD = 0.26, 95% CI: -0.07-0.58, P = 0.127). Patients with AD or MCI did not significantly differ from controls of blood vitamin B12 levels, AD (SMD = -0.05, 95% CI: -0.19-0.08, P = 0.440), or MCI (SMD = 0.01, 95% CI: -0.16-0.17, P = 0.94). Some cohort studies have suggested that higher Hcy, methionine, and S-adenosylmethionine levels may accelerate cognitive decline in patients with MCI or AD, and vitamin B12 deficiency is a risk factor for the disease; however, the results of other studies were inconsistent. According to the GRADE system, all these outcomes scored very low to low quality, and no high-quality evidence was found. CONCLUSION Only Hcy levels in the plasma and serum were found to be inversely related to the risk of AD. However, due to the low quality of supporting these results, high-quality studies are needed to verify these findings. SYSTEMATIC REVIEW REGISTRATION http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022308961.
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Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.