Catherine M. Milte

Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial.

Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA + 0·16 g DHA/d; n 17), DHA (1·55 g DHA + 0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P=0·04) and DHA (P=0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P=0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P=0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.

Nutritional modulation of cognitive function and mental health

The important role of diet in cardiometabolic health is generally well recognised; for mental health, it is not so well understood. However, lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease, but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components - antioxidants, omega-3 fatty acids and B vitamins - in the brain and, hence, modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health.

Oiling the Brain: A Review of Randomized Controlled Trials of Omega-3 Fatty Acids in Psychopathology across the Lifespan

Around one in four people suffer from mental illness at some stage in their lifetime. There is increasing awareness of the importance of nutrition, particularly omega-3 polyunsaturated fatty acids (n-3 PUFA), for optimal brain development and function. Hence in recent decades, researchers have explored effects of n-3 PUFA on mental health problems over the lifespan, from developmental disorders in childhood, to depression, aggression, and schizophrenia in adulthood, and cognitive decline, dementia and Alzheimer’s disease in late adulthood. This review provides an updated overview of the published and the registered clinical trials that investigate effects of n-3 PUFA supplementation on mental health and behavior, highlighting methodological differences and issues.

Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood lipid levels

Consumption of long-chain n-3 PUFA, particularly DHA, has been shown to improve cardiovascular risk factors but the intake required to achieve benefits is unclear. We sought to determine the relationship between DHA intake, increases in erythrocyte DHA content and changes in blood lipids. A total of sixty-seven subjects (thirty-six male, thirty-one female, mean age 53 years) with fasting serum TAG > or = 1.1 mmol/l and BMI>25 kg/m(2) completed a 12-week, randomized, double-blind, placebo-controlled parallel intervention. Subjects consumed 2, 4 or 6 g/d of DHA-rich fish oil (26 % DHA, 6 % EPA) or a placebo (Sunola oil). Fasting blood lipid concentrations and fatty acid profiles in erythrocyte membranes were assessed at baseline and after 6 and 12 weeks. For every 1 g/d increase in DHA intake, there was a 23 % reduction in TAG (mean baseline concentration 1.9 (sem 0.1) mmol/l), 4.4 % increase in HDL-cholesterol and 7.1 % increase in LDL-cholesterol. Erythrocyte DHA content increased in proportion to the dose of DHA consumed (r 0.72, P < 0.001) and the increase after 12 weeks was linearly related to reductions in TAG (r - 0.38, P < 0.01) and increases in total cholesterol (r 0.39, P < 0.01), LDL-cholesterol (r 0.33, P < 0.01) and HDL-cholesterol (r 0.30, P = 0.02). The close association between incorporation of DHA in erythrocytes and its effects on serum lipids highlights the importance of erythrocyte DHA as an indicator of cardiovascular health status.

Polyunsaturated fatty acid status in attention deficit hyperactivity disorder, depression, and Alzheimer's disease: towards an omega-3 index for mental health?

Interest in the role of polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) omega-3 (n-3) PUFAs, in mental health is increasing. This review investigates whether n-3 PUFA levels are abnormal in people with three prevalent mental health problems - attention deficit hyperactivity disorder, depression, and dementia. Data sources included PubMed, Web of Science, and bibliographies of papers published in English that describe PUFA levels in the circulation of individuals who have these mental health conditions. Although abnormal blood PUFA levels were reported in a number of studies, weighted comparisons of PUFA status showed no significant differences overall between people with mental health problems and controls. Whether those with low n-3 PUFA status are likely to be more responsive to n-3 PUFA supplementation is not yet resolved. Further studies assessing PUFA levels and mental status with greater uniformity are required in order to clarify the relationship between LC n-3 PUFA status and mental health.

Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls

Polyunsaturated fatty acid (PUFA) levels are altered in adults with cognitive decline and also depression. Depression facilitates progression from mild cognitive impairment (MCI) to dementia. We investigated associations between omega-3 (n-3) and omega-6 (n-6) PUFAs and cognition, memory and depression in 50 adults ≥65 years with MCI and 29 controls. Memory, depressive symptoms and erythrocyte PUFAs (% total fatty acids) were assessed. Eicosapentaenoic acid (EPA) was lower in MCI vs controls (.94% vs 1.26%, p<.01); n-6 PUFAs were higher: dihomo-gamma-linolenic acid (1.51% vs 1.32%, p<.01), arachidonic acid (11.54% vs 10.70%, p<.01), n-6 docosapentaenoic acid (DPA:.46% vs.34%, p<.01), and total n-6 PUFA (24.14% vs 23.37%, p<.05). Higher n-6 DPA predicted poorer mental health. Lower n-3 DPA was associated with higher self-reported bodily pain. Adults with MCI had higher depression scores (3.05±.39 vs 1.33±.24, p<.01). Depressive symptoms associated with elevated n-6 PUFA may contribute to cognitive decline in this population.

Dose-dependent increases in heart rate variability and arterial compliance in overweight and obese adults with DHA-rich fish oil supplementation.

Heart rate (HR) variability and large arterial compliance can be improved using fish oils. DHA, a component of fish oil, has cardiovascular health benefits, but its effect on HR variability (HRV) and arterial compliance is yet to be quantified. Sixty-seven overweight or obese adults (thirty-six males and thirty-one females; 53 (sem 2) year; BMI 31.7 (sem 1.1) kg/m(2)) were randomly allocated to consume either 6 g/d sunola oil (control; n 17), fish oil (260 mg DHA+60 mg EPA per g) at doses of 2 g/d (n 16), 4 g/d (n 17) or 6 g/d (n 17). Blood pressure, HR and compliance of large and small arteries were measured while supine at baseline and after 12 weeks in all participants, and HRV was assessed in a subgroup of forty-six participants. There was no effect of fish oil on blood pressure, small artery compliance or HR. However, the low frequency:high frequency ratio of HRV decreased with increasing doses of fish oil (r - 0.34, P = 0.02), while large artery compliance increased (r 0.34, P = 0.006). Moreover, the changes in these biomarkers were significantly correlated (r - 0.31, P = 0.04) and may reflect fish oil-induced improvements in arterial function and cardiac autonomic regulation.

Associations of diet quality with health-related quality of life in older Australian men and women

This study investigated associations between diet quality measures and quality of life two years later. Adults 55-65 years participating in the Wellbeing, Eating and Exercise for a Long Life (WELL) study in Victoria, Australia (n = 1150 men and n = 1307 women) completed a postal survey including a 111-item food frequency questionnaire in 2010. Diet quality in 2010 was assessed via the dietary guideline index (DGI), recommended food score (RFS) and Mediterranean diet score (MDS). The RAND 36-item survey assessed health-related quality of life in 2012. Associations were assessed using logistic regression adjusted for covariates. In men, DGI and RFS were associated with better reported energy (OR = 1.79, CI: 1.25, 2.55 and OR = 1.56, CI: 1.11, 2.19 respectively), and DGI was additionally associated with better general health (OR = 1.54, 95% CI: 1.08, 2.20), and overall mental component summary scale (OR = 1.51, CI: 1.07, 2.15) in the fully adjusted model. In women, associations between two indices of diet quality (DGI, RFS) physical function (OR = 1.66, CI: 1.19, 2.31 and OR = 1.70, CI: 1.21, 2.37 respectively) and general health (OR = 1.83, CI: 1.32, 2.54 and OR = 1.54, CI: 1.11, 2.14 respectively) were observed. DGI was also associated with overall physical component summary score (OR = 1.56, CI: 1.12, 2.17). Additional associations between emotional wellbeing and DGI (OR = 1.40, CI: 1.01, 1.93) and RFS (OR = 1.44, CI: 1.04, 1.99), and MDS and energy (OR = 1.53, CI: 1.11, 2.10) were observed in the fully adjusted model, in women only. Older adults with better quality diets report better health-related quality of life, with additional associations with emotional wellbeing observed in women.

Telomere shortening in elderly individuals with mild cognitive impairment may be attenuated with ω-3 fatty acid supplementation: A randomized controlled pilot study

OBJECTIVES Excessive shortening of the telomeric ends of chromosomes is a marker of accelerated aging. Oxidative stress and nutritional deficiency may influence this process. The aim of this study was to investigate the effect of ω-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on telomeric shortening in elderly individuals with mild cognitive impairment (MCI). METHODS Thirty-three adults ages > 65 y with MCI were randomized to receive a supplement rich in the long-chain ω-3 PUFAs eicosapentaenoic acid (EPA; 1.67 g EPA + 0.16 g docosahexaenoic acid DHA/d; n = 12) or DHA (1.55 g DHA + 0.40 g EPA/d; n = 12), versus ω-6 PUFA linoleic acid (LA; 2.2 g/d; n = 9) for 6 mo. RESULTS The intervention did not show an increase in telomere length with treatment and there was a trend toward telomere shortening during the intervention period. Linear mixed modeling produced a robust model although statistically underpowered. Telomere shortening was greatest in the LA group (d = 0.21) than in the DHA (d = 0.12) and EPA groups (d = 0.06). Increased erythrocyte DHA levels were associated with reduced telomere shortening (r = -0.67; P = 0.02) in the DHA group. CONCLUSION Telomeric shortening may be attenuated by ω-3 PUFA supplementation, requiring further investigation in larger samples.

Polyunsaturated fatty acids, cognition and literacy in children with ADHD with and without learning difficulties

Suboptimal omega-3 polyunsaturated fatty acid (n-3 PUFA) levels may contribute to attention deficit hyperactivity disorder (ADHD) and related developmental problems. Associations between n-3 and omega-6 (n-6) PUFA levels in red blood cells (erythrocytes) and learning and behaviour were investigated in 75 children aged 7–12 with ADHD. Children provided blood samples and underwent cognitive assessments. Parents completed questionnaires and Conners’ Rating Scales. Controlling for covariates, higher n-3 PUFA predicted lower anxiety/shyness (β = -.27), higher docosahexaenoic acid (DHA) better word reading (β = .22), and higher n-6 PUFA poorer reading (β = -.34), vocabulary (β = .-.26), spelling (β = -.30) and attention (β = -.30). Thirty-six per cent of the sample with learning difficulties had lower DHA than those without (M = 3.26 ± 0.54 vs M = 3.68 ± 0.76, p = .02). This study is the first to compare erythrocyte PUFAs (a measure of PUFA status) in children who have ADHD with and without learning difficulties, and supports emerging indications that the former may be more likely responders to n-3 PUFAs.