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Diabetes Care Feb 2021Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3...
Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.
OBJECTIVE
Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.
RESEARCH DESIGN AND METHODS
We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.
RESULTS
The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.
CONCLUSIONS
High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
Topics: Adult; Animals; Cohort Studies; Diabetes Mellitus; Diet; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Phospholipids; Prospective Studies
PubMed: 33303636
DOI: 10.2337/dc20-1463 -
The Cochrane Database of Systematic... Dec 2020Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been...
BACKGROUND
Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition.
OBJECTIVES
To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease.
SEARCH METHODS
We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review.
SELECTION CRITERIA
We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks.
DATA COLLECTION AND ANALYSIS
Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD.
MAIN RESULTS
We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid.
AUTHORS' CONCLUSIONS
Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.
Topics: Alzheimer Disease; Bias; Cognition; Dementia; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Phospholipids; Placebos; Prodromal Symptoms; Randomized Controlled Trials as Topic; Time Factors
PubMed: 33320335
DOI: 10.1002/14651858.CD011679.pub2 -
Journal of the American Heart... Nov 2022Background Utility of high-density lipoprotein cholesterol (HDL-C) in assessing the antiatherogenic properties of HDL may be limited in midlife women. Novel metrics of...
Background Utility of high-density lipoprotein cholesterol (HDL-C) in assessing the antiatherogenic properties of HDL may be limited in midlife women. Novel metrics of HDL function, lipid contents, and subclasses may better reflect the atheroprotective capacities of HDL, supporting the need to evaluate how cardiovascular health affects these metrics in women. We assessed the relationship of early midlife Life's Simple 7 (LS7) score and its health behavior components with future HDL function (HDL-cholesterol efflux capacity), HDL-phospholipid, HDL-triglyceride, HDL particles (HDL-P) and size, and the relationship between LS7 score and changes in HDL metrics over time. Methods and Results We analyzed 529 women (baseline age: 46.4 [2.6] years, 57% White) from the SWAN HDL (Study of Women's Health Across the Nation HDL) study who had baseline LS7 followed by future repeated HDL metrics. Multivariable linear mixed models were used. Higher LS7 score was associated with favorable future HDL profile (higher HDL-phospholipid, total HDL-P and large HDL-P, lower HDL-triglyceride, and larger overall HDL size). Ideal body mass index was associated with higher HDL-cholesterol efflux capacity, HDL-phospholipid, and large HDL-P, lower HDL-triglyceride and small HDL-P, and larger overall HDL size. Ideal physical activity was associated with higher HDL-phospholipid, and total, large, and medium HDL-P. Ideal smoking was associated with less HDL-triglycerides. Diet was not related to HDL metrics. Higher LS7 score and ideal body mass index were associated with slower progression of HDL size over time. Conclusions Novel HDL metrics may better reflect the clinical utility of HDL. Improving lifestyle at midlife, particularly maintaining ideal body mass index, is associated with better future HDL phenotype.
Topics: Female; Humans; Blood Pressure; Blood Glucose; Cholesterol; Body Mass Index; Phospholipids; Risk Factors; Cardiovascular Diseases
PubMed: 36285790
DOI: 10.1161/JAHA.122.026243 -
Nutrition Journal Oct 2017Previously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and...
BACKGROUND
Previously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and was inversely associated with T2D, while a "traditional" pattern (rich in fish, palm oil, plantain, green-leafy vegetables, beans, garden egg, fermented maize products,) increased the odds of T2D. To investigate, if specific fatty acids (FAs), partly reflecting the intakes of certain food groups and cooking methods, might explain the observed diet-disease relationships, serum phospholipid fatty acid profiles were characterized and their relationships with blood lipids that are common risk factors for T2D were analyzed.
METHODS
The relative proportions of 28 FAs (%) in 653 Ghanaians without T2D were measured by gas chromatography. In a cross-sectional analysis, the associations of FAs with dietary patterns and with serum lipids that are likely involved in T2D development were investigated. The FAs distributions across dietary pattern scores were examined. Standardized beta coefficients (β) were calculated for the associations of dietary pattern scores (per 1 standard deviation (SD) increase) with FAs. Across the tertiles of selected diet-related FAs, adjusted means of serum triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol were calculated.
RESULTS
In this mainly female (76%), middle-aged (mean age: 46.4, SD: 15.3 years) and predominately overweight study population (mean body mass index: 25.8, SD: 5.4 kg/m), saturated FAs (SFAs) contributed 52% to total serum FAs, n-6 polyunsaturated FAs (PUFAs) 27%, monounsaturated FAs 12%, n-3 PUFAs 9% and trans FAs (TFAs) <1%. The "purchase" pattern was related to lower proportions of n-3 PUFAs (β per 1 score SD: -0.25, p < 0.0001), but higher proportions of linoleic acid (LA) (β per 1 score SD: 0.24, p < 0.0001). The "traditional" pattern was characterized by lower proportions of arachidic acid (β per 1 score SD: -0.10, p = 0.001). LA was inversely associated with triglycerides, but positively with HDL-cholesterol and LDL-cholesterol.
CONCLUSIONS
In this Ghanaian population, serum FA profiles reflected the intake of key components of dietary patterns, such as fish and vegetable oil. FAs from manufactured foods (SFAs) and deep-fried meals (TFAs) did not contribute to the observed associations between dietary patterns and T2D. Still, LA might partly explain the health-beneficial effect of the "purchase" pattern.
Topics: Adult; Body Mass Index; Cholesterol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Ghana; Humans; Male; Middle Aged; Phospholipids; Risk Factors; Trans Fatty Acids; Triglycerides
PubMed: 28969694
DOI: 10.1186/s12937-017-0286-x -
Scientific Reports May 2024This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g,...
This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g, mean ± SD, CV = 0.16), and to explore the potential for interactions between dietary cholesterol and phospholipid. An 8-week experiment was conducted using six experimental feeds containing three supplemental cholesterol concentrations (0, 0.2 and 0.4% dry matter) at two supplemental phospholipid concentrations (0% and 1.0% dry matter). Dietary cholesterol concentrations of ≥ 0.2% resulted in up to threefold greater weight gain compared to 0% dietary cholesterol, but without any significant main or interactive dietary phospholipid effect. An interaction was observed for lobster survival with lowest survival (46%) recorded for combined 0% cholesterol and 0% phospholipid compared to every other treatment (71-100%). However, all surviving lobsters at 0% dietary cholesterol, regardless of dietary phospholipid level, were in poor nutritional condition. Apparent feed intake (AFI) was significantly higher at dietary cholesterol ≥ 0.2% but was lower for each corresponding dietary cholesterol level at 1% dietary phospholipid. This implied that the feed conversion ratio was improved with supplemental phospholipid. In conclusion, this study confirms the essential nature of dietary cholesterol and that dietary phospholipid can provide additional benefits.
Topics: Animals; Phospholipids; Cholesterol, Dietary; Palinuridae; Animal Feed; Animal Nutritional Physiological Phenomena
PubMed: 38710742
DOI: 10.1038/s41598-024-60367-1 -
The Journal of Nutrition Mar 2021Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate,...
BACKGROUND
Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear.
OBJECTIVES
We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases.
METHODS
RAW 264.7 cells were exposed to 65 μg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets.
RESULTS
We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment.
CONCLUSIONS
Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.
Topics: Animals; Chromatography, Liquid; Lipid Metabolism; Macrophages; Mass Spectrometry; Metabolic Diseases; Metabolomics; Mice; Models, Animal; Oleic Acid; Phospholipids; Pioglitazone; Pyrimidines; RAW 264.7 Cells
PubMed: 33571370
DOI: 10.1093/jn/nxaa411 -
Nutrients Aug 2023The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective...
BACKGROUND
The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
METHODS
The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort ( = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels.
RESULTS
Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain -3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for -3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)).
CONCLUSIONS
Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.
Topics: Humans; Fatty Acids; Phospholipids; Prospective Studies; Neoplasms; Fatty Acids, Omega-3; Trans Fatty Acids
PubMed: 37686727
DOI: 10.3390/nu15173695 -
Cells Dec 2020Lipids are important molecules for human health. The quantity and quality of fats consumed in the diet have important effects on the modulation of both the natural... (Review)
Review
Lipids are important molecules for human health. The quantity and quality of fats consumed in the diet have important effects on the modulation of both the natural biosynthesis and degradation of lipids. There is an important number of lipid-failed associated metabolic diseases and an increasing number of studies suggesting that certain types of lipids might be beneficial to the treatment of many metabolic diseases. The aim of the present work is to expose an overview of biosynthesis, storage, and degradation of lipids in mammalian cells, as well as, to review the published data describing the beneficial effects of these processes and the potential of some dietary lipids to improve metabolic diseases.
Topics: Adipose Tissue; Animals; Biomarkers; Cholesterol; Diet; Dietary Fats; Eicosanoids; GTP Phosphohydrolases; Homeostasis; Humans; Lipid Metabolism; Metabolic Diseases; Mitochondrial Proteins; Phospholipids; Sterols; Triglycerides
PubMed: 33291746
DOI: 10.3390/cells9122605 -
Nature Metabolism Feb 2021Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting...
Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting factors responsible for poor CNS repair are only partially understood. Here, we test the impact of a Western diet (WD) on phagocyte function in a mouse model of demyelinating injury that requires microglial innate immune function for a regenerative response to occur. We find that WD feeding triggers an ageing-related, dysfunctional metabolic response that is associated with impaired myelin-debris clearance in microglia, thereby impairing lesion recovery after demyelination. Mechanistically, we detect enhanced transforming growth factor beta (TGFβ) signalling, which suppresses the activation of the liver X receptor (LXR)-regulated genes involved in cholesterol efflux, thereby inhibiting phagocytic clearance of myelin and cholesterol. Blocking TGFβ or promoting triggering receptor expressed on myeloid cells 2 (TREM2) activity restores microglia responsiveness and myelin-debris clearance after demyelinating injury. Thus, we have identified a druggable microglial immune checkpoint mechanism regulating the microglial response to injury that promotes remyelination.
Topics: Aging; Animals; Cholesterol; Demyelinating Diseases; Diet; Diet, Western; Immunity, Innate; Liver X Receptors; Lysophosphatidylcholines; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Microglia; Myelin Sheath; Phagocytes; Receptors, Immunologic; Transforming Growth Factor beta
PubMed: 33619376
DOI: 10.1038/s42255-021-00341-7 -
Scientific Reports Jun 2023Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD,...
Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration. In this study, we tested the hypothesis that enriching retinal DHA through a novel dietary approach could ameliorate symptoms of retinopathy in 5XFAD mice, a widely employed model of AD. The results show that 5XFAD mice have significantly lower retinal DHA compared to their wild type littermates, and feeding the lysophosphatidylcholine (LPC) form of DHA and eicosapentaenoic acid (EPA) rapidly normalizes the DHA levels, and increases retinal EPA by several-fold. On the other hand, feeding similar amounts of DHA and EPA in the form of triacylglycerol had only modest effects on retinal DHA and EPA. Electroretinography measurements after 2 months of feeding the experimental diets showed a significant improvement in a-wave and b-wave functions by the LPC-diet, whereas the TAG-diet had only a modest benefit. Retinal amyloid β levels were decreased by about 50% by the LPC-DHA/EPA diet, and by about 17% with the TAG-DHA/EPA diet. These results show that enriching retinal DHA and EPA through dietary LPC could potentially improve visual abnormalities associated with AD.
Topics: Mice; Animals; Docosahexaenoic Acids; Eicosapentaenoic Acid; Lysophosphatidylcholines; Alzheimer Disease; Amyloid beta-Peptides; Retina; Retinal Diseases; Diet
PubMed: 37280266
DOI: 10.1038/s41598-023-36268-0