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Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick, RP
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33(2):1554-1564
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Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive memory loss, spatial disorientation, cognitive impairment and behavioural changes. Ageing is the main risk factor for AD, with approximately one-third of Americans over the age of 85 being affected by the condition. The APOE gene provides instructions for making the apolipoprotein E family of proteins that are involved in fat metabolism and cholesterol transport. There are three different variants of this gene, one inherited from each parent. The variant called APOE4 is thought to increase AD risk from 2-3-fold (one inherited copy) to as much as 15-fold (two inherited copies), compared to individuals who do not carry this variant. The omega-3 oil docosahexaenoic acid (DHA) is an essential fatty acid, which comprises approximately 30% of the fats found in the human brain. Low levels of DHA in the brain increase the risk of developing AD, while normal and high levels may prevent the condition and ameliorate symptoms. This review paper brings together several lines of evidence on why individuals with the APOE4 gene variant don’t respond well to DHA supplementation but experience positive effects from dietary intake of DHA. The author suggests that this is due to the different forms of DHA found in dietary and supplemental sources. Some of the DHA present in fish and seafood is in phospholipid form, which is metabolised into lysophosphatidylcholine DHA (DHA-lysoPC) in the body. In contrast, fish oil supplements contain no DHA in phospholipid form, but in other forms that are mostly metabolised to free DHA. This paper puts forward an argument that, due to the breakdown of the integrity of the blood-brain barrier, APOE4 carriers have impaired brain transport of free DHA but not DHA-lysoPC. The author concludes that dietary sources that contain high amounts of DHA in phospholipid form, such as fish and fish roe may help increase plasma levels of DHA-lysoPC, which may be better transported to the brains of APOE4 carriers. She also highlights the pressing need for future clinical trials to evaluate the effects of omega-3 oils in phospholipid form on the cognitive function of APOE4 carriers with AD.
Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
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Effect of Nut Consumption on Erectile and Sexual Function in Healthy Males: A Secondary Outcome Analysis of the FERTINUTS Randomized Controlled Trial.
Salas-Huetos, A, Muralidharan, J, Galiè, S, Salas-Salvadó, J, Bulló, M
Nutrients. 2019;11(6)
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National Institutes of Health define erectile dysfunction as a persistent difficulty achieving and maintaining an erection sufficient for satisfactory sexual intercourse. The main aim of the study was to explore the effects of nuts supplementation on erectile function determined by the International Index of Erectile Function and the endothelial (inner lining of blood vessels) function. The study is a randomised controlled, two-interventions parallel, clinical trial conducted in healthy males who reported a Western-style diet. The 119 participants were randomly assigned to one of the two interventions. Results indicate that adding 60 g/d of mixed raw nuts to a Western-style diet for 14-wk improved the auto-reported orgasmic function and sexual desire parameters in a group of healthy reproductive-aged participants compared with an age-matched control group. Authors conclude that compliance with a healthy diet supplemented with mixed nuts may help to improve erectile and sexual desire.
Abstract
Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets. In the present study, we evaluated the effects of mixed nuts supplementation on erectile and sexual function. Eighty-three healthy male aged 18-35 with erectile function assessment were included in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial. Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of nuts (nut group; n = 43), or (2) the usual Western-style diet avoiding nuts (control group; n = 40). At baseline and the end of the intervention, participants answered 15 questions contained in the validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical characteristics, and seminogram and blood biochemical parameters did not differ between intervention groups at baseline. Compared to the control group, a significant increase in the orgasmic function (p-value = 0.037) and sexual desire (p-value = 0.040) was observed during the nut intervention. No significant differences in changes between groups were shown in peripheral concentrations of NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic function and sexual desire.
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Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.
Fitzgerald, KC, Vizthum, D, Henry-Barron, B, Schweitzer, A, Cassard, SD, Kossoff, E, Hartman, AL, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
Multiple sclerosis and related disorders. 2018;23:33-39
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Multiple sclerosis (MS) is a disease of the central nervous system. Dietary modification is emerging as a safe intervention to potentially modify disease course. The main aim of this study was to assess the safety and feasibility of an intermittent fasting diet in people with MS. Secondary outcomes explored the effects of calorie restriction (CR) diets on body weight and anthropometric characteristics as well as on patient-reported outcomes including fatigue, sleep and mood. The study is a pilot randomised controlled feeding study of three different types of diets. Each participant (n=36) was randomized to 1 of 3 diets: a control diet (placebo), a daily CR diet and intermittent CR diet. Results indicate that daily CR diet was associated with marginally greater weight loss than the intermittent CR diet. Both CR diets were associated with trends toward improvements in cardiometabolic outcomes. Furthermore, CR diets were associated with in improvements in emotional well-being. Authors conclude that CR and weight loss represent interventions for clinically relevant symptoms due to MS, such as emotional well-being, without adding meaningful risks or adverse outcomes.
Abstract
An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.
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Prevalence and determinants of physical activity in a mixed sample of psychiatric patients in Saudi Arabia.
Alosaimi, FD, Abalhasan, MF, Alhabbad, AA, Fallata, EO, Haddad, BA, AlQattan, NI, Alassiry, MZ
Saudi medical journal. 2018;39(4):401-411
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Physical activity has been shown to considerably reduce the burden of several non-communicable disorders (are diseases of long duration and generally slow progression), such as heart disease, stroke, diabetes, and breast and colon cancers. The aim of the study is to estimate the prevalence of physical activity among a mixed group of patients with psychiatric illnesses in Saudi Arabia. Furthermore, the study sought to evaluate the associations between physical activity, patients with different psychiatric diagnoses and the use of psychotropic medications. The study is a cross-sectional observational study that recruited 1185 patients seeking psychiatric advice, with an average age of 38.0±13.0 years. Results indicate a low prevalence of physical activity in a large, mixed sample of patients with psychiatric illnesses in both inpatient and outpatient settings in Saudi Arabia. Authors conclude that physical activity levels vary according to the type of psychiatric disease and the medications used. They outline that it is important to assess the physical activity status in patients with psychiatric illnesses and promote physical activity programs among psychiatric patients.
Abstract
OBJECTIVES To estimate prevalence of physical activity and its associations with various psychiatric disorders and the use of psychotropic medications. METHODS A cross-sectional observational study was carried out between July 2012 and June 2014. Patients were enrolled from a number of hospitals located in 5 regions of the Kingdom of Saudi Arabia. RESULTS A total of 1185 patients were included in current analysis: 796 were outpatients, and 389 were inpatients. Out of 1,185 patients, 153 (12.9%) were physically active. Much higher rates of physical activity were reported among males than females (15.9% versus 9.6%, p less than 0.001). According to the univariate analysis, higher rates of physical activity were positively correlated with primary bipolar disorders, the use of antianxiety medications and, to a lesser extent, use of antipsychotic medications, but they were negatively correlated with primary anxiety disorders, use of antidepressant medications, and use of multiple psychotropic medications. The associations between physical activity and primary bipolar disorders (odds ratio [OR]=2.47, p=0.002), use of antianxiety medications (OR=3.58, p=0.003), and use of multiple psychotropic medications (OR=0.33, p less than 0.001) remained significant after adjusting for demographic and clinical characteristics. CONCLUSION We report a variable but generally low prevalence of physical activity among a large, mixed sample of psychiatric patients in Saudi Arabia. These findings may highlight the importance of assessing physical activity status of psychiatric patients and the critical need for physical activity promotion programs among this group of disadvantaged patients.