No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial.

Low dietary intakes of the n-3 long-chain PUFA (LCPUFA) EPA and DHA are thought to be associated with increased risk for a variety of adverse outcomes, including some psychiatric disorders. Evidence from observational and intervention studies for a role of n-3 LCPUFA in depression is mixed, with some support for a benefit of EPA and/or DHA in major depressive illness. The present study was a double-blind randomised controlled trial that evaluated the effects of EPA+DHA supplementation (1.5 g/d) on mood and cognitive function in mild to moderately depressed individuals. Of 218 participants who entered the trial, 190 completed the planned 12 weeks intervention. Compliance, confirmed by plasma fatty acid concentrations, was good, but there was no evidence of a difference between supplemented and placebo groups in the primary outcome - namely, the depression subscale of the Depression Anxiety and Stress Scales at 12 weeks. Mean depression score was 8.4 for the EPA+DHA group and 9.6 for the placebo group, with an adjusted difference of - 1.0 (95 % CI - 2.8, 0.8; P = 0.27). Other measures of mood, mental health and cognitive function, including Beck Depression Inventory score and attentional bias toward threat words, were similarly little affected by the intervention. In conclusion, substantially increasing EPA+DHA intake for 3 months was found not to have beneficial or harmful effects on mood in mild to moderate depression. Adding the present result to a meta-analysis of previous relevant randomised controlled trial results confirmed an overall negligible benefit of n-3 LCPUFA supplementation for depressed mood.

Depressed mood and n-3 polyunsaturated fatty acid intake from fish: non-linear or confounded association?

There is increasing evidence of an association between low dietary intake of essential n-3 long chain polyunsaturated fatty acids (n-3 EFAs) and depressed mood. This study aimed to evaluate this association in a large population-based sample of UK individuals. N-3 EFA intake (intake from fish alone, and from all sources (fish and supplements)), depressed mood (assessed using the short-form Depression, Anxiety and Stress Scales) and demographic variables (sex, age, Index of Multiple Deprivation (IMD) based on postal code, and date of questionnaire completion) were obtained simultaneously by self-report questionnaire (N = 2982). Using polynomial regression, a non-linear relationship between depressed mood and n-3 EFA intake from fish was found, with the incremental decrease in depressed mood diminishing as n-3 EFA intake increased. However, this relationship was attenuated by adjustment for age and IMD. No relationship between depression and n-3 EFA intake from all sources was found. These findings suggest that higher levels of n-3 EFA intake from fish are associated with lower levels of depressed mood, but the association disappears after adjustment for age and social deprivation, and after inclusion of n-3 EFA intake from supplements. This study does have a number of limitations, but the findings available suggest that the apparent associations between depressed mood and n-3 EFA intake from fish may simply reflect a wider association between depressed mood and lifestyle.

Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials.

BACKGROUND: Greater dietary intakes of n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for depressed mood. OBJECTIVE: This study aimed to systematically review all published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood. DESIGN: Eight medical and health databases were searched over all years of records until June 2006 for trials that exposed participants to n-3 PUFAs or fish, measured depressed mood, were conducted on human participants, and included a comparison group. RESULTS: Eighteen randomized controlled trials were identified; 12 were included in a meta-analysis. The pooled standardized difference in mean outcome (fixed-effects model) was 0.13 SDs (95% CI: 0.01, 0.25) in those receiving n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I2 = 79%, P < 0.001). The presence of funnel plot asymmetry suggested that publication bias was the likely source of heterogeneity. Sensitivity analyses that excluded one large trial increased the effect size estimates but did not reduce heterogeneity. Meta-regression provided some evidence that the effect was stronger in trials involving populations with major depression-the difference in the effect size estimates was 0.73 (95% CI: 0.05, 1.41; P = 0.04), but there was still considerable heterogeneity when trials that involved populations with major depression were pooled separately (I2 = 72%, P < 0.001). CONCLUSIONS: Trial evidence that examines the effects of n-3 PUFAs on depressed mood is limited and is difficult to summarize and evaluate because of considerable heterogeneity. The evidence available provides little support for the use of n-3 PUFAs to improve depressed mood. Larger trials with adequate power to detect clinically important benefits are required.

Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction.

RATIONALE: It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. OBJECTIVES: To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. METHODS: Participants were moderate to moderate-high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. RESULTS: Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. CONCLUSIONS: The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.

Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence.

RATIONALE: Many studies have found that caffeine consumed after overnight caffeine abstinence improves cognitive performance and mood. Much less is known, however, about the effects of caffeine after shorter periods of caffeine abstinence. OBJECTIVES: The aim of this study was to measure the effects on psychomotor and cognitive performance, mood, hand steadiness, blood pressure and heart rate of caffeine administration after periods of 4, 6, and 8 h of caffeine abstinence. METHODS: Participants (n = 49, 27 female) were moderate to moderate-high caffeine consumers (mean daily intake 370 mg/day). Following overnight caffeine abstinence, a 'pre-dose' of caffeine (1.2 mg/kg) was administered at 9 A.M, 11 A.M or 1 P.M. The participants started a baseline battery of measurements at 4 P.M.: before receiving caffeine (1.2 mg/kg) or placebo at 5 P.M.: They then performed the battery of tests again, starting at 5:30 P.M. This was a double-blind, placebo-controlled, randomised study. RESULTS: Performance and mood measurements confirmed a psychostimulant action of caffeine (versus placebo), but only after 8 h of caffeine abstinence. Caffeine also increased blood pressure after 8-h abstinence, whereas hand steadiness was decreased and perception of task demand was increased by caffeine after 4 h, but not after 6- and 8-h abstinence. CONCLUSIONS: A second cup-of-coffee equivalent dose of caffeine only reliably affected cognitive performance and mood after an 8-h interval between doses, but not after shorter intervals (when caffeine had some adverse effects). These results show that, apart from caffeine consumption soon after waking, the daily pattern of caffeine intake of many typical caffeine consumers is not well explained by the short-term psychostimulant effects of caffeine.