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The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis.
Fairbairn, P, Dyall, SC, Tsofliou, F
The British journal of nutrition. 2023;129(3):428-441
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Due to the insidious onset, cognitive impairment often goes unnoticed for several years, with clinical diagnosis being made late into the disease progression. Cognition is critical for functional independence as people age, and intact cognition is vital for humans to communicate effectively. The aims of this study were to (i) investigate whether supplementation with a combination of omega-3 polyunsaturated fatty acids (n-3 PUFA) and B vitamins alone or as part of a multi-nutrient formula can prevent cognitive decline in older adults, and (ii) determine whether the effects of a single nutrient intervention with either n-3 PUFA or B vitamins could be modified by the status of the other nutrient. This study is a systematic review and meta-analysis of fourteen studies of which eleven were randomised controlled trials and the rest were post hoc analysis of randomised controlled trials. Results show a benefit of supplementing with nutrient formulas that contain both n-3 PUFA and B vitamins on global cognition and episodic memory with small to moderate effect sizes. In fact, they can help preserve cognition in the older adults. Authors conclude that more experimental work providing a combination of nutrients including both n-3 PUFA and B vitamins, in healthy older adults or those showing early signs of cognitive decline, is clearly warranted to better explore how nutrition can impact the trajectory of cognition in older adults.
Abstract
There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60-70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.
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Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions.
Dyall, SC, Balas, L, Bazan, NG, Brenna, JT, Chiang, N, da Costa Souza, F, Dalli, J, Durand, T, Galano, JM, Lein, PJ, et al
Progress in lipid research. 2022;:101165
Abstract
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.
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Effects of a high-DHA multi-nutrient supplement and exercise on mobility and cognition in older women (MOBILE): a randomised semi-blinded placebo-controlled study.
Fairbairn, P, Tsofliou, F, Johnson, A, Dyall, SC
The British journal of nutrition. 2020;:1-10
Abstract
There is a complex interplay between mobility and cognition in older adults. We have previously shown that a high-DHA multi-nutrient supplement improves habitual walking speed, verbal memory and psychomotor response latency in older women. Exercise also improves mobility and cognition in older adults, and n-3 fatty acids and exercise share a range of overlapping biological effects. This study examined for the first time the effects of the high-DHA multi-nutrient supplement and aerobic exercise on mobility and cognition in older women. Women (mean age 67 (sd 8) years) were assigned to the following groups: multi-nutrient (1 g DHA, 160 mg EPA, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20 mg d-α tocopherol, 1 mg folic acid and 20 µg vitamin B12 per d, n 13), multi-nutrient and exercise (spin class twice per week, n 14), exercise and placebo (n 12) or placebo (n 12). The multi-nutrient was given for 24 weeks and exercise for 12 weeks. No treatment effects were observed for the primary outcome, habitual walking speed. Improvements in verbal memory and executive function were seen for all treatments groups v. placebo (all, P < 0·05). Significant improvements in self-reported emotional well-being were seen with multi-nutrient and exercise groups v. placebo (P = 0·03). The results suggest that the high-DHA multi-nutrient supplement produces similar improvements in cognitive function to aerobic exercise, offering the intriguing prospect that supplementation may be able to mitigate some of the effects of low physical activity on cognitive function in the elderly.
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Combining a high DHA multi-nutrient supplement with aerobic exercise: Protocol for a randomised controlled study assessing mobility and cognitive function in older women.
Fairbairn, P, Tsofliou, F, Johnson, A, Dyall, SC
Prostaglandins, leukotrienes, and essential fatty acids. 2019;:21-30
Abstract
There is a complex interplay between cognition and gait in older people, with declines in gait speed coexisting with, or preceding cognitive decline. Omega-3 fatty acids, B vitamins, vitamin E, phosphatidylserine, and Ginkgo Biloba show promise in preserving mobility and cognitive function in older adults. Exercise benefits mobility and there is evidence suggesting positive interactions between exercise and omega-3 fatty acids on physical and cognitive function in older adults. Non-frail or pre-frail females aged ≥60 years are included in a randomized placebo controlled study. Intervention groups are: high DHA multi-nutrient supplement and exercise, placebo supplement and exercise, high DHA multi-nutrient supplement, and placebo supplement. Dietary supplementation is 24 weeks. The exercise intervention, two cycle ergometer classes per week, is for the final 12 weeks. The primary outcome is habitual walking speed, secondary outcomes include gait variables under single and dual task, five times sit to stand, verbal and spatial memory, executive function, interference control and health related quality of life. Blood fatty acids, serum homocysteine, dietary intake, physical activity, and verbal intelligence are measured to assess compliance and control for confounding factors. The study is registered at www.clinicaltrials.gov (NCT03228550).
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Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA.
Dyall, SC
Frontiers in aging neuroscience. 2015;:52
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer's disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.