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Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.
Dupont, J, Wauters, E, Dedeyne, L, Vercauteren, L, Amini, N, Lapauw, L, Matthys, C, Verschueren, S, Tournoy, J, Koppo, K, et al
BMC geriatrics. 2023;23(1):272
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Diet plays an important role in the development and treatment of sarcopenia, the age-related loss of muscle mass and function. Besides protein intake, the intake of polyunsaturated fatty acids (PUFAs) is also suggested to influence muscle physiology and sarcopenia progression. The aim of this study was to assess the dietary intake of PUFAs and PUFAs status in a sample of well-defined sarcopenic older adults. This study was a secondary, exploratory, cross-sectional analysis of 29 older adults (aged 65 years or older) with sarcopenia. Results showed that omega-3 PUFAs intake was low in older adults with sarcopenia. Moreover, PUFAs intake and status did not correspond well in this population. Authors concluded that intake or status of omega-3 was positively associated with measures of sarcopenia, whereas intake of omega-6 was negatively associated.
Abstract
AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.
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A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.
Vauzour, D, Scholey, A, White, DJ, Cohen, NJ, Cassidy, A, Gillings, R, Irvine, MA, Kay, CD, Kim, M, King, R, et al
The American journal of clinical nutrition. 2023;118(2):369-381
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At a population level, interventions that delay the onset of dementia by 2 years are predicted to reduce the number of dementia patients by 20%. Prospective cohort studies have consistently reported cognitive and neurophysiological benefits of the fish-derived omega-3 long-chain polyunsaturated fatty acids (PUFAs), EPA, and DHA and plant-derived flavanols (FLAVs). This study hypothesised that 12-month administration of a combination of 500 mg cocoa FLAVs with 1.5g omega-3 long-chain PUFAs would improve cognitive function in a mixed subjective cognitive impairment and mild cognitive impairment cohort. This study is based on the results of the CANN randomised controlled trial. A total of 258 participants were recruited and randomised to control or test intervention. Following baseline measurements, 125 participants were randomised into the active OM3FLAV intervention group and 121 into the control group. Results showed that the 1-year intervention with EPA and DHA and cocoa FLAVs did not improve cognition or protect the brain against atrophy in older adults with evidence of memory deficits. Authors concluded that given the complexity of neuropathological processes underpinning cognitive decline and dementia risk, multidomain, multinutrient, or whole diet approaches may be needed to positively impact the cognitive trajectory in the medium term (months to 3 years).
Abstract
BACKGROUND There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.
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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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Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder.
Cussotto, S, Delgado, I, Oriolo, G, Kemper, J, Begarie, D, Dexpert, S, Sauvant, J, Leboyer, M, Aouizerate, B, Martin-Santos, R, et al
Depression and anxiety. 2022
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Major depressive disorder (MDD) is a leading cause of disability, and antidepressant drug treatment is only effective in over half of patients with a high prevalence of treatment resistance. The importance of nutrition in mental health is gaining recognition. Omega-3 is an essential polyunsaturated fatty acid (PUFA) vital for anti-inflammatory processes and brain integrity. In the absence of the body's ability to make Omega-3, it or its precursors must be acquired from the diet. Yet altered metabolic pathways can hamper the process and the adequate balance with PUFA Omega‐6 is also crucial, as elevated levels of Omega-6 are linked to several diseases. An extensive amount of research suggests that higher Omega-3 levels reduce the occurrence of depression. Yet results using just Omega-3s for depression have been varied. This European-wide study sought to investigate how the PUFA status could affect the clinical response to treatment with antidepressants. 60-adults with an average age of 41 with major depressive disorders received antidepressive treatment. Their red blood cell fatty acids content was determined, and at the end of the 8-week trial treatment responders and non-responders were identified. Findings affirmed the existing knowledge that depressive symptoms are strongly associated with PUFA status. Patients who did not respond to treatment showed low levels of Omega-3 and an unfavourable ratio of Omega-3 to Omega-6 at the start of treatment. Higher levels of Omega-3 fatty acid of DHA seemed to produce a better clinical response to treatments than the Omega-3 of EPA. The authors discussed some potential mechanisms and suggested that PUFA intake and metabolism could be a potential tool for the management of treatment-unresponsive patients with depression. This review highlights the clinical importance of considering PUFA status and metabolism in the support of major depressive disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Healthy eating such as that with low omega-6 diets has more than a physiological result on the human body and carries significant biochemical consequences when the omega-6 to omega-3 ratio is deemed to be ‘high’.
- The result of this research has pharmaceutical implications - if the findings could be imparted to the general public in layman’s terms, practitioners could empower individuals to take greater control of their mental health through more naturalistic means, i.e., optimised nutrition.
- There are wider cognitive considerations of healthy eating beyond that of treating Major Depressive Disorder due to implicated blood-brain-barrier effects, as concluded in this study.
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:
Sixty adults suffering from major depressive disorder (MDD) were recruited into a multicenter study assessing the impact of baseline polyunsaturated (PUFA) levels on responsiveness to antidepressants. Neuropsychiatric evaluations producing MADRS (Montgomery Åsberg Depression Rating Scale) scores at baseline, four weeks and again at eight weeks, were performed. The pre-recorded baseline PUFA levels were then used as an associative and predictive indicator when viewing the end point scoring of participants, thus categorising into responsive and nonresponsive strata.
Of those with low omega-3 and high omega-6 to omega-3 ratio at baseline, there was increased association with ‘non-responsive’ classification at end point (week 8). Participants were deemed ‘non-responsive’ to anti-depressant treatment when scores at week 8 failed to demonstrate ≥50% reduction in MADRS scoring.
Clinical practice applications:
- Clinicians could monitor MDD within at-risk-groups, such as those who are overweight (mean BMI of ALL study participants was 24.20 kg/m2 with a standard deviation of 4.21) or those experiencing an inflammatory state with blood-brain-barrier involvement, as part of a mental ill-health prevention programme.
- When presenting with symptoms of major depressive disorder and prescribing antidepressants, clinicians could recommend increasing consumption of foods high in omega-3 and/or querying the patient about their dietary habits.
- Article supports recommendations for an increase in the consumption of omega-3 rich foods amongst the general population to prevent or intervene in cases of major depressive disorder.
- Wider cognitive implications beyond major depressive disorder in the presence of low omega-3, such as cognitive decline as seen with dementia, theorised due to altered blood-brain-barrier (Cussotto et al., 2022; Gustafson et al., 2020).
Considerations for future research:
- Repeated studies, with normalised distribution of antidepressant and sample size by country, with greater geographic inclusion, along with age categorisation. The broader geographic inclusion is necessary to rule out cultural diets as a confounding variable. An example of how different cultural diets could influence the results, which has potentially been highlighted in this study, is the more predominant consumption of a Mediterranean diet which may have been the case for the participants from Spain or, as could also be the case, an underlying vitamin D deficiency of the participants from Germany.
- Novel studies for assessing diet against mood could be beneficial to fully apply the findings of this study to clinical practice applications and that of the practice of nutritional therapists. The thinking here is the potential for anti-inflammatory foods inducing better mood results through gut-brain axis links and resultant influence on microbiome.
Abstract
BACKGROUND Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. METHODS Sixty depressed adults who met criteria for MDD according to DSM-IV-TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non-responders (NR) based on their MADRS (Montgomery-Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. RESULTS Lower ω-3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω-3 index; and higher ω-6/ω-3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω-3 index and ω-6/ω-3 ratio significantly predicted response to antidepressants at study endpoint. CONCLUSIONS These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.
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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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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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Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.
Schutte, S, Esser, D, Siebelink, E, Michielsen, CJR, Daanje, M, Matualatupauw, JC, Boshuizen, HC, Mensink, M, Afman, LA
The American journal of clinical nutrition. 2022;116(1):132-150
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Energy restriction (ER) diets are considered an effective strategy for managing obesity and preventing or reducing the risk of associated comorbidities. However, there are very few previous studies comparing the quality of energy restriction diets and their effect on maximising the health benefits. Therefore, this 12-week, parallel-designed, randomised controlled trial compared the effects of a 25% high-quality ER diet with a 25% low-quality ER diet and a habitual diet on cardiometabolic risk factors of 110 participants with abdominal obesity. Both ER diets were nutritionally balanced. The high-quality ER diet had added Monounsaturated fatty acids (MUFAs), Omega-3 Polyunsaturated fatty acids (n-3 PUFAs), fibre, and plant protein and had less fructose in it. The low-quality ER diet contained Saturated fatty acids (SFAs) and monosaccharides such as fructose. At the end of the 12-week trial, participants on the 25% high-quality diet showed more promising results in weight loss, reduction in cholesterol and triglycerides, and adipose tissue gene expression of energy metabolism pathways compared to the 25% low-quality ER diet. Insulin-sensitive participants with abdominal obesity on a 25% high-quality diet lost more weight compared to the rest of the participants. Further robust studies are required to evaluate the findings due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the beneficial effects of an ER diet when it is enriched with specific nutrients.
Abstract
BACKGROUND Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.
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Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.
Holm Nielsen, S, Sardar, S, Siebuhr, AS, Schlemmer, A, Schmidt, EB, Bay-Jensen, AC, Karsdal, MA, Christensen, JH, Kristensen, S
Rheumatology international. 2021;41(6):1065-1077
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Psoriatic arthritis is a chronic inflammatory condition that causes joint pain and swelling along with red, flaky, and scaly skin. Inflammation affects the extracellular matrix, which comprises proteins and molecules that support cartilage, bone, and soft tissues in joints. A high level of collagen fragments is released into the bloodstream as a result. Fish oils and fish are good sources of n-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid and docosahexaenoic acid. Inflammation and joint pain have been shown to be reduced by n-3 PUFA in previous studies. This randomised, double-blinded, placebo-controlled study randomly assigned 142 patients with psoriatic arthritis to receive 3g n-3 PUFA (50% EPA and 50% DHA) or 3g of olive oil as the control for 24 weeks. Taking N-3 PUFA supplementation did not affect extracellular matrix turnover in psoriatic arthritis patients. This may be due to the anti-inflammatory properties of olive oil, which was used as a control, and to the short duration of the study. The benefits of using n-3 PUFA as a therapeutic strategy in patients with psoriatic arthritis need to be evaluated in larger, robust long-term studies. Furthermore, the clinical efficacy of n-3 PUFA cannot be distinguished since 75% of the patients took anti-rheumatic drugs. A study like this can provide healthcare professionals with insights into the potential benefits of n-3 PUFAs, which may aid them in making therapeutic decisions.
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.
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A Low ω-6 to ω-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth.
Van Name, MA, Savoye, M, Chick, JM, Galuppo, BT, Feldstein, AE, Pierpont, B, Johnson, C, Shabanova, V, Ekong, U, Valentino, PL, et al
The Journal of nutrition. 2020;150(9):2314-2321
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Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of fat in the liver of people who drink very little or no alcohol. NAFLD is a common problem in children with obesity and diet is a contributory factor. Recent research has suggested that the Western diet and its high omega-6 and low omega-3 fat intakes may lead to the development of NAFLD. This quasi-experimental study of twenty children with obesity and NAFLD aimed to determine whether 12 weeks of low omega-6: omega-3 ratio diet affected liver fat content. The results showed that the diet did not affect weight loss but still significantly decreased liver fat content, with one third of the participants returning their liver fat content to normal. In lieu of weight loss, improvements were also observed in markers for liver function, diabetes and blood cholesterol. Interestingly those who carry a certain gene increasing their risk of developing NAFLD, showed greater improvements in liver fat percentage and liver function. It was concluded that in the absence of weight loss, a diet high in omega-3 and low in omega-6 improves fatty liver disease, risk factors for heart disease and has the potential to revert liver fat content to normal levels. This study could be used by healthcare professionals to recommend a low omega-6:omega-3 diet in children with obesity and NAFLD.
Abstract
BACKGROUND Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth. OBJECTIVES We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response. METHODS In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used. RESULTS Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time. CONCLUSIONS These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.