Increasing rates of suicide among military personnel are of great concern to the Department of Defense. We evaluated the serum fatty acid status from n=800 Military suicide deaths and n=800 matched controls. We found that that all US Military personnel studied had low levels of docosahexaenoic acid and with in this narrow range, the lowest levels were associated with a75% increase in the risk of suicide death. We are proposing to evaluate if restoring adequate omega-3 fatty acid nutritional status can reduce or prevent neuropsychiatric harm among military personnel. In Oct 2009, we organized an international workshop entitled """"""""Nutritional Armor for the Warfighter: Can Omega-3 Fatty Acids Enhance Resilience, Wellness and Optimize Performance"""""""". In conjunction with this conference we modeled fatty acid intake of a typical US Garrison diet and modeled enhancement of the omega-3 content of this diet to deliver our estimations of adequate daily intakes of long chain omega-3 fats. The conclusions of this workshop has reached the US Army Surgeon general and the Chairman of the Joint Chiefs of Staff who have directed further evaluation of this issue. Dietary intakes that meet criteria for Recommended Daily Intakes (RDAs) have been calculated from two sources of data: cross-national data sets and the ALSPAC cohort study. Dose response relationships were derived comparing greater intake of seafood and lower prevalence rates of four psychiatric disorders and lower mortality rates of eight major causes. These publications are the only calculations of DRI's for long chain omega-3 fatty acids that utilize the Institute of Medicine statistical methodologies. Chronic excessive alcohol consumption depletes brain stores of omega-3 fatty acids which are necessary for optimal neural function. In our ongoing clinical trial of aggressive alcoholics, we determine if treatment with 2.8 g/d of omega-3 fatty acids will reduce 1) aggressive behaviors, 2) improve neurochemical measures of serotonergic function as well as other neurotransmitters associated with impulsivity and alcohol use 3) reduce measures of craving 4) reduce risk of relapse. This protocol is active and has enrolled 96 subjects with 100% tracking of data. Preliminary results indicate that anger is reduced by 33% (p<0.0008) in 12 weeks. An unexpected finding was the substantial reduction of heavy drinking days among recovering alcoholics. Those compliant with the protocol in the active group drank 3.2 days/90 while those compliant in the placebo group drank 17 days/ 90. This indicates that treatment with omega-3 fatty acids may have an effect size of 8.4. In comparison the effect size of Naltrexone, also used for relapse prevention is 0.2. These findings complement a placebo controlled clinical trial conducted with collaboration with Laure-Budens Branchey, M.D., among polysubstance dependent subjects where omega-3 fatty acids reduced anger scores by 50% over 4 months. We have collaborated with Marc Schuckit, M.D and Jean Golding, Ph.D. in designing a study to prospectively capture initial drinking behavior of these children as they enter adolescence. If this is identified as a risk factor, prevention studies can be planned. A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. We evaluated the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom, the Avon Longitudinal Study of Parents and Children (ALSPAC). The subjects were 156 boys (54.5%) and girls who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. Results: The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. These data can be evaluated to determine if inadequate intakes of omega-3 fatty acids during pregnancy or early childhood is a risk factor for future substance abuse. In collaboration with Barbara Gracious, MD, we evaluated a randomized placebo controlled trial of flax oil among children with bipolar disorder. We found that when plasma levels of eicosapentaenoic acid rose, the children had substantially fewer severe psychiatric symptoms. These data indicate that supporting the omega-3 status of these children can substantially complement pharmacological therapies. Mothers can become depleted of omega-3 essential fatty acids during pregnancy when their dietary intake is inadequate. Dietary deficiencies may increase the risk of depressive symptoms for the mothers. Preliminary data is available from an open trial of omega-3 fatty acids among women with depression during pregnancy currently being conducted in collaboration with Marlene Freeman, MD at the University of Arizona. Depressive symptoms were reduced an average of 43.5 % during 8 weeks of treatment. These findings are significant as they offer a treatment for depression during pregnancy that is not only non-toxic, but has additional health benefits to pregnant women and their babies. These findings are being followed up with a randomized, controlled trial which has enrolled n=60 subjects. The results of these interventional trials were predicted from data from an epidemiological study of the dietary intake of omega-3 fatty acids during pregnancy among nearly 14,500 women enrolled in ALSPAC. Findings were robust after rigorous examination of potential confounding factors. Previously we found that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates neurodevelopmental harm to the children. The children of mothers who ate seafood below the limit advised had greater risks of peer problems, poor prosocial behaviors and low verbal IQ. The work was conducted in collaboration with the ALSPAC study and examined nearly 9,000 children. These data have formed the core of an FDA model that reevaluates both the risks and benefits of seafood consumption in pregnancy, issued 15 JAN 2009. Appropriate modeling of risks and benefits of seafood consumption requires large numbers of samples Tissue compositional data of trace metals (MeHg,Se,Pb,Fe and Cd) n=5,853 and essential fatty acids umbilical cord blood samples (n=4,090). Analyses of these data should inform public advisories of regarding risks and benefits of fish consumption during pregnancy.

Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2011
Total Cost
$366,148
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
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Zip Code
Hibbeln, Joseph R; Northstone, Kate; Evans, Jonathan et al. (2018) Vegetarian diets and depressive symptoms among men. J Affect Disord 225:13-17
Hibbeln, Joseph; Gregory, Steven; Iles-Caven, Yasmin et al. (2018) Total mercury exposure in early pregnancy has no adverse association with scholastic ability of the offspring particularly if the mother eats fish. Environ Int 116:108-115
Strandjord, Sarah E; Lands, Bill; Hibbeln, Joseph R (2018) Validation of an equation predicting highly unsaturated fatty acid (HUFA) compositions of human blood fractions from dietary intakes of both HUFAs and their precursors. Prostaglandins Leukot Essent Fatty Acids 136:171-176
Golding, Jean; Rai, Dheeraj; Gregory, Steven et al. (2018) Prenatal mercury exposure and features of autism: a prospective population study. Mol Autism 9:30
Lepsch, Jaqueline; Farias, Dayana Rodrigues; Eshriqui, Ilana et al. (2018) Serum fatty acids are positively associated with changes in systemic blood pressure throughout pregnancy. Pregnancy Hypertens 13:7-13
Mann, John Douglas; Faurot, Keturah R; MacIntosh, Beth et al. (2018) A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol. Prostaglandins Leukot Essent Fatty Acids 128:41-52
Freitas-Vilela, Ana Amélia; Pearson, Rebecca M; Emmett, Pauline et al. (2018) Maternal dietary patterns during pregnancy and intelligence quotients in the offspring at 8 years of age: Findings from the ALSPAC cohort. Matern Child Nutr 14:
Portnoy, Jill; Raine, Adrian; Liu, Jianghong et al. (2018) Reductions of intimate partner violence resulting from supplementing children with omega-3 fatty acids: A randomized, double-blind, placebo-controlled, stratified, parallel-group trial. Aggress Behav :
Raine, Adrian; Ang, Rebecca P; Choy, Olivia et al. (2018) Omega-3 (?-3) and social skills interventions for reactive aggression and childhood externalizing behavior problems: a randomized, stratified, double-blind, placebo-controlled, factorial trial. Psychol Med :1-10
Gow, Rachel V; Heron, Jon; Hibbeln, Joseph R et al. (2018) Maternal fish consumption during pregnancy and smoking behavioural patterns. Br J Nutr 119:1303-1311

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