-
Frontiers in Neurology 2023There is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders-in particular, mild cognitive impairment (MCI), Alzheimer's...
BACKGROUND
There is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders-in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)-following a proof-of-concept study in Parkinson's disease published in 2005.
METHODS
To provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials.
RESULTS
10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class "B" evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class "U" evidence (unproven) for cognitive stabilization in individuals with mild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class "C" evidence (possibly effective) for improvement of non-motor features and class "U" evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance.
CONCLUSIONS
Limitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary.
PubMed: 36846143
DOI: 10.3389/fneur.2023.1123290 -
Advances in Nutrition (Bethesda, Md.) May 2023To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed,... (Meta-Analysis)
Meta-Analysis Review
To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed, Scopus, and ISI Web of Science of relevant articles published before November 2021. Randomized controlled trials (RCTs) evaluating the effects of soluble fibers on blood lipids in adults were included. We estimated the change in blood lipids for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the mean difference (MD) and 95% CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias and certainty of the evidence was evaluated using the Cochrane risk of bias tool and the Grading Recommendations Assessment, Development, and Evaluation methodology, respectively. A total of 181 RCTs with 220 treatment arms (14,505 participants: 7348 cases and 7157 controls) were included. There was a significant reduction in LDL cholesterol (MD: -8.28 mg/dL, 95% CI: -11.38, -5.18), total cholesterol (TC) (MD: -10.82 mg/dL, 95% CI: -12.98, -8.67), TGs (MD: -5.55 mg/dL, 95% CI: -10.31, -0.79), and apolipoprotein B (Apo-B) (MD: -44.99 mg/L, 95% CI: -62.87, -27.12) after soluble fiber supplementation in the overall analysis. Each 5 g/d increase in soluble fiber supplementation had a significant reduction in TC (MD: -6.11 mg/dL, 95% CI: -7.61, -4.61) and LDL cholesterol (MD: -5.57 mg/dl, 95% CI: -7.44, -3.69). In a large meta-analysis of RCTs, results suggest that soluble fiber supplementation could contribute to the management of dyslipidemia and the reduction of cardiovascular disease risk.
Topics: Adult; Humans; Cholesterol, LDL; Randomized Controlled Trials as Topic; Lipids; Dyslipidemias; Dietary Supplements
PubMed: 36796439
DOI: 10.1016/j.advnut.2023.01.005 -
Journal of Genetic Counseling Apr 2023Geographical ancestry has been associated with an increased risk of various genetic conditions. Race and ethnicity often have been used as proxies for geographical...
Geographical ancestry has been associated with an increased risk of various genetic conditions. Race and ethnicity often have been used as proxies for geographical ancestry. Despite numerous problems associated with the crude reliance on race and ethnicity as proxies for geographical ancestry, some genetic testing in the clinical, research, and employment settings has been and continues to be race- or ethnicity-based. Race-based or race-targeted genetic testing refers to genetic testing offered only or primarily to people of particular racial or ethnic groups because of presumed differences among groups. One current example is APOL1 testing of Black kidney donors. Race-based genetic testing raises numerous ethical and policy questions. Given the ongoing reliance on the Black race in genetic testing, it is important to understand the views of people who identify as Black or are identified as Black (including African American, Afro-Caribbean, and Hispanic Black) regarding race-based genetic testing that targets Black people because of their race. We conducted a systematic review of studies and reports of stakeholder-engaged projects that examined how people who identify as or are identified as Black perceive genetic testing that specifically presumes genetic differences exist among racial groups or uses race as a surrogate for ancestral genetic variation and targets Black people. Our review identified 14 studies that explicitly studied this question and another 13 that implicitly or tacitly studied this matter. We found four main factors that contribute to a positive attitude toward race-targeted genetic testing (facilitators) and eight main factors that are associated with concerns regarding race-targeted genetic testing (barriers). This review fills an important gap. These findings should inform future genetic research and the policies and practices developed in clinical, research, public health, or other settings regarding genetic testing.
Topics: Humans; Apolipoprotein L1; Attitude; Black People; Ethnicity; Genetic Testing
PubMed: 36644818
DOI: 10.1002/jgc4.1653 -
Journal of the Academy of Nutrition and... Feb 2024Avocados are a rich source of unsaturated fats and bioactives, however, their role in altering cardiometabolic risk factors is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Avocados are a rich source of unsaturated fats and bioactives, however, their role in altering cardiometabolic risk factors is unclear.
OBJECTIVE
The aim was to review the effects of consuming diets containing avocado compared with control diets containing no or low amounts of avocado on cardiometabolic risk factors in adults who were healthy, had clinical cardiovascular disease, or were at increased risk of cardiovascular disease.
METHODS
Five electronic databases were searched (PubMed, Web of Science, Scopus, ProQuest, and a Clinical Trials Registry) along with Google Scholar to identify studies published between January 1990 and November 10, 2021. Randomized controlled trials ≥3 weeks and prospective cohort studies were included. Ten studies-9 randomized controlled trials (n = 503 participants) and 1 prospective observational study (n = 55,407)-met the inclusion criteria. Outcomes assessed by means of meta-analysis were low-density lipoprotein cholesterol (LDL-C) (primary), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Outcomes assessed by narrative review were TC to HDL-C ratio, non-HDL-C, apolipoprotein B, blood pressure, body weight, body mass index (calculated as kg/m), waist circumference, waist-to-hip ratio, body composition, and blood glucose and insulin concentrations. Risk of bias was assessed using the Cochrane Risk of Bias tool, version 2.0 and Newcastle-Ottawa Scale; quality of evidence was examined using the Grading of Recommendations, Assessment, Development and Evaluation method. Random-effects models meta-analyses were performed when there were ≥3 studies of the same design (ie, randomized controlled trial) and reporting the same outcome. Statistical heterogeneity was assessed by calculating χ and I statistics and publication bias was assessed by funnel plots.
RESULTS
Overall, there was a small, significant reduction in TC (-5.08 mg/dL [to convert to mmol/L, divide by 38.67]; 95% CI -9.29 to -0.87 mg/dL; P = .02) in avocado vs the control groups and no significant difference in LDL-C, HDL-C, or triglycerides. Subgroup analysis demonstrated significant reductions in LDL-C (-9.4 mg/dL [to convert to mmol/L, divide by 38.67]; 95% CI -10.84 to -7.95 mg/dL; P < .00001) and TC (-7.54 mg/dL; 95% CI -9.40 to -5.68 mg/dL; P < .00001) in avocado vs control groups in hypercholesterolemic populations, and no differences were seen in normocholesterolemic populations. However, the certainty in the findings was graded as low to very low. Body weight and composition were not negatively affected by avocado consumption.
CONCLUSIONS
Avocado consumption may reduce TC and LDL-C in people with hypercholesterolemia. Avocado consumption does not negatively impact body weight. Larger, well-conducted studies are needed to have greater confidence in the role of avocado consumption on cardiovascular disease risk factors.
Topics: Adult; Humans; Persea; Cardiovascular Diseases; Cholesterol, LDL; Prospective Studies; Cholesterol; Triglycerides; Body Weight; Cholesterol, HDL; Observational Studies as Topic
PubMed: 36565850
DOI: 10.1016/j.jand.2022.12.008 -
Vision (Basel, Switzerland) Dec 2022Serum apolipoproteins have been reported as a more significant marker for diabetic retinopathy (DR) compared with serum cholesterols. This article aims to review the... (Review)
Review
Serum apolipoproteins have been reported as a more significant marker for diabetic retinopathy (DR) compared with serum cholesterols. This article aims to review the associations between serum cholesterols and apolipoproteins, and the presence and severity of DR. The protocol of this systematic review was registered at the PROSPERO registry (CRD42022303331). We conducted a systematic search of literature published between 2011 to 2022 using the search terms "serum cholesterol" AND/OR "lipoprotein" AND/OR "apolipoprotein" AND/OR "diabetic retinopathy". Fifteen studies were included in this review. Six studies assessed the association between serum cholesterols, apolipoproteins, and the presence of DR. Three studies reported lower levels of apolipoprotein A1, and one study reported higher levels of apolipoprotein B in patients with DR. The remaining nine studies compared serum cholesterol and apolipoprotein levels according to DR severity. Patients with more severe grades of DR presented with lower apolipoprotein A1 in six (66.7%) studies, higher apolipoprotein B levels in seven (77.8%) studies, and a higher apolipoprotein B/apolipoprotein A1 ratio in six out of seven (85%) studies. In conclusion, serum apolipoproteins, in particular the apolipoprotein B/apolipoprotein A1 ratio, were a more consistent marker for DR severity compared with serum cholesterols.
PubMed: 36548939
DOI: 10.3390/vision6040077 -
Dementia & Neuropsychologia Dec 2022Mild cognitive impairment (MCI) is an interstitial state between normal aging and dementia. (Review)
Review
Working memory assessment using cambridge neuropsychological test automated battery can help in the diagnosis of mild cognitive impairment: a systematic review and meta-analysis.
UNLABELLED
Mild cognitive impairment (MCI) is an interstitial state between normal aging and dementia.
OBJECTIVE
In this study, we investigated working memory (WM) profiles of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB). We also examined the diagnostic accuracy and possible associated factors as secondary outcomes of the study.
METHODS
We conducted an electronic search on EMBASE, PubMed, and ScienceDirect databases. Studies with MCI participants and using CANTAB battery subtests for the assessment of WM were included. Meta-analysis was conducted using the CMA2 software.
RESULTS
Out of 1537 records, 14 studies were covered in this systematic review, and 7 of them were included in the meta-analysis. There was a significant difference between MCI patients and healthy controls in spatial working memory (SWM) (SDM: 0.535; 95%CI 11-96; p-value=0.014), spatial span (SSP) (SDM: 0.649 95%CI 0.297-0.100; p-value<0.01), and rapid visual information processing (RVP) (SDM: 0.52; 95%CI 0.386-0.654; p-value<0.01). WM function of MCI patients was associated with the cerebrospinal fluid (CSF) levels of tau-protein and amyloid-beta (Aβ).
CONCLUSIONS
WM is an impaired cognitive domain in MCI. CANTAB WM subtests including SSP, SWM, and RVP are accurate enough to be used as a proper assessment tool for the diagnosis of MCI in clinical settings. Tau-protein and Aβ are associated with lower WM scores in MCI patients; however, sex, age, psychiatric disorders, apolipoprotein 4 allele, and functional activity scores cannot affect WM.
PubMed: 36530766
DOI: 10.1590/1980-5764-dn-2022-0006 -
Cardiovascular Diabetology Dec 2022Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of... (Review)
Review
Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.
Topics: Humans; Apolipoprotein C-I; Atherosclerosis; Cholesterol Ester Transfer Proteins; Diabetes Mellitus; Inflammation; Lipoproteins, HDL; Lipoproteins, VLDL; Triglycerides
PubMed: 36471375
DOI: 10.1186/s12933-022-01703-5 -
Frontiers in Nutrition 2022The findings of trials investigating the effect of conjugated linoleic acid (CLA) administration on lipid profile are controversial. This meta-analysis of randomized...
BACKGROUND
The findings of trials investigating the effect of conjugated linoleic acid (CLA) administration on lipid profile are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on lipid profile.
METHODS
Two authors independently searched electronic databases including PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. The random effects model was used to evaluate the mean and standard deviation.
RESULTS
In total, 56 RCTs with 73 effect sizes met the inclusion criteria and were eligible for the meta-analysis. CLA supplementation significantly alter triglycerides (TG) (WMD: 1.76; 95% CI: -1.65, 5.19), total cholesterols (TC) (WMD: 0.86; 95% CI: -0.42, 2.26), low-density lipoprotein cholesterols (LDL-C) (WMD: 0.49; 95% CI: -0.75, 2.74), apolipoprotein A (WMD: -3.15; 95% CI: -16.12, 9.81), and apolipoprotein B (WMD: -0.73; 95% CI: -9.87, 8.41) concentrations. However, CLA supplementation significantly increased the density lipoprotein cholesterol (HDL-C) (WMD: -0.40; 95% CI: -0.72, -0.07) concentrations.
CONCLUSION
CLA supplementation significantly improved HDL-C concentrations, however, increased concentrations of TG, TC, LDL-C, apolipoprotein A, and apolipoprotein B.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022331100.
PubMed: 36438733
DOI: 10.3389/fnut.2022.953012 -
Frontiers in Nutrition 2022Omega-3 fatty acids (OM3-FA), a promising treatment for high triglycerides, have gradually attracted public attention. However, some studies showed that their...
The effect of omega-3 fatty acids and its combination with statins on lipid profile in patients with hypertriglyceridemia: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND/AIM
Omega-3 fatty acids (OM3-FA), a promising treatment for high triglycerides, have gradually attracted public attention. However, some studies showed that their application presented tricky problems, like increasing low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to systematically evaluate the effect of OM3-FA or their combination with statins on the lipid profile in patients with hypertriglyceridemia.
MATERIALS AND METHODS
This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) guidelines. PubMed, Embase, Web of science, and Cochrane library were searched up to May 15, 2022. The random-effects model was applied to calculate the mean difference (MD) and associated 95% confidence intervals (CI).
RESULTS
This meta-analysis included 32 studies with 15,903 subjects. When OM3-FA was used as monotherapy compared with placebo, it significantly decreased TG (MD: -39.81, 95% CI: -54.94 to -24.69; < 0.001), TC (MD: -2.98, 95% CI: -5.72 to -0.25, = 0.03), very low-density lipoprotein cholesterol (VLDL-C) (MD: -25.12, 95% CI: -37.09 to -13.14; < 0.001), and non-high-density lipoprotein cholesterol (non-HDL-C) levels (MD: -5.42, 95% CI: -8.06 to-2.78; < 0.001), and greatly increased LDL-C (MD: 9.10, 95% CI: 4.27 to 13.94; < 0.001) and HDL levels (MD: 1.60, 95% CI: 0.06 to 3.15; = 0.04). Regarding apolipoprotein B (Apo-B) and apolipoprotein AI (Apo-AI), no significant effect was identified. When OM3-FA was combined with statins, significant reductions were observed in the concentrations of TG (MD: -29.63, 95% CI: -36.24 to -23.02; < 0.001), TC (MD: -6.87, 95% CI: -9.30 to -4.45, < 0.001), VLDL-C (-20.13, 95% CI: -24.76 to -15.50; < 0.001), non-HDL-C (MD: -8.71, 95% CI: -11.45 to -5.98; < 0.001), Apo-B (MD: -3.50, 95% CI: -5.37 to -1.64; < 0.001), and Apo-AI (MD: -2.01, 95% CI: -3.07 to -0.95; < 0.001). However, the combined therapy did not exert significant changes on the levels of high-density lipoprotein cholesterol (HDL-C) and LDL-C compared to control group.
CONCLUSION
The use of OM3-FA either as monotherapy or in combination with statins may potentially reduce the levels of TG, TC, VLDL-C, non-HDL-C, Apo-B, and Apo-AI while increasing the levels of LDL-C and HDL-C. Nevertheless, the effects of OM3-FA observed in this review should be interpreted with caution due to the high heterogeneity between the included studies.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022329552].
PubMed: 36313109
DOI: 10.3389/fnut.2022.1039056 -
Biomolecules Oct 2022Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including... (Review)
Review
Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin ( or ) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood-brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the transporter and -linked molecular mechanisms at the BBB interface in the pathogenesis of AD.
Topics: Humans; Clusterin; Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Membrane Transport Proteins; Lipids
PubMed: 36291661
DOI: 10.3390/biom12101452