EPA Eases Anxiety in Substance Abusers
Various studies have implicated low fish consumption or reduced blood levels of long-chain omega-3 fatty acids (n-3 LC-PUFAS) in the occurrence of various psychiatric disorders, alcoholism and among substance abusers. It has been known since 1996 that n-3 PUFAs, especially eicosapentaenoic acid (EPA), are reduced in major depression. A recent post-mortem analysis reported significantly lower levels of cortex docosahexaenoic acid (DHA) in patients with major depressive disorder. Clinical trials using n-3 LC-PUFAs or purified EPA or DHA to treat a variety of mental disorders have generally, but not always, reported favorable outcomes. It is unclear whether both EPA and docosahexaenoic acid (DHA) are effective and if so, what a suitable dose range is for each fatty acid. For example, some studies in depressed patients have used high doses (>6 g/day), while others reported that 1 g/day was effective, but doses of 2 to 4 g/day were less so. In a pilot study among substance abusers, supplementation with 3 g/day of EPA+DHA for 3 months was associated with reduced anxiety scores. In one report, both n-3 and n-6 PUFAs were significantly lower in substance abusers who relapsed compared with those who did not.
This study reports the associations between changes in anger and anxiety scores and serum levels of EPA and DHA in 22 substance abusers who consumed about 3 g/day of n-3 LC-PUFAs or soybean oil for 3 months. The n-3 LC-PUFA capsules provided 2.2 g/day of EPA, 500 mg/day DHA, and 50 mg of n-3 docosapentaenoic acid and alpha-linolenic acid. Participants were enrolled in an outpatient substance abuse program in Brooklyn, New York, and were free of major psychiatric and physical illnesses and had liver function tests no greater than 1 SD above maximum normal values.
Participants completed a dietary history questionnaire and a modified version of the Profiles of Mood States questionnaire 1, 2 and 3 months following the start of the study and gave blood samples at the beginning and end of the study. Fatty acids were determined in plasma. The Profiles in Mood States includes scores for anger, anxiety, depression, vigor, confusion and fatigue. Eight patients received methadone treatment and 5 took antidepressants in stable doses throughout the study. Participants did not differ at baseline in body mass index, energy consumption or low intake of n-3 LC-PUFAs.
After 3 months of treatment, participants consuming the n-3 LC-PUFAs had a significant decline in their anger scores, whereas scores in those taking the placebo capsules increased slightly. Scores reached their maximum after 2 months of n-3 LC-PUFA consumption. Anger scores continued to decline throughout the 3-month period for those on the active n-3 LC-PUFA treatment. A similar pattern of significantly improved anxiety scores was observed for substance abusers consuming the n-3 LC-PUFAs, but scores were unchanged in those taking the placebo.
When the investigators examined the relationship between the anger and anxiety scores at the end of the study with the percent change in plasma fatty acids over the 3-month study, they observed significant associations (Figure 1). Lower anger scores were associated with increased DHA, n-3 docosapentaenoic acid and total n-3 LC-PUFAs, but not with increased EPA concentrations. In contrast, reduced anxiety was associated with increased EPA, but not with changes in DHA. Changes in anger and anxiety scores were not associated with changes in any n-6 PUFAs.
It is worth noting that improved scores for anger and anxiety related to increased DHA and EPA, respectively, but neither behavior related to both DHA and EPA when these fatty acids were examined individually. However, both behaviors were significantly associated with increases in the total concentration of n-3 LC-PUFAs measured in µg/ml.
Only a few studies have reported an association between low plasma DHA and hostility in violent men and young urban males. Students under the stress of school exams who consumed 1.5 to 1.8 g/day of DHA exhibited no aggression against others compared with increased aggression observed in those taking a placebo. This study adds another link between DHA and aggressive behavior as reflected in anger scores.
As with anger, studies of anxiety and n-3 PUFAs are scarce. A few have suggested a link between increased anxiety and low levels of EPA or n-3 LC-PUFAs. The administration of a mixture of n-3 and n-6 PUFAs to anxious college students was associated with improved appetite, mental concentration and academic organization. Patients with social anxiety disorder had significantly lower concentrations of n-3 PUFAs compared with those not having this disorder. Moderate fish consumption (83 to 112 g/day or 3 to 4 oz/day) or n-3 LC-PUFA intake was associated with a significant 30% lower risk of incurring depression, anxiety or stress in a 2-yr prospective study of Spanish adults. The present report identified increased EPA specifically with improved anxiety scores and higher DHA with less anger.
Although it may be tempting to suggest that EPA and DHA influence anxiety and anger behaviors through different mechanisms, and plausible explanations could be proffered, these specific associations need more robust confirmation before reaching firm conclusions. Investigation of EPA and DHA administered individually without the other would be useful across an array of mental disorders. This study supports others in demonstrating that anxious or angry substance abusers who have low blood levels of n-3 LC-PUFAs achieve significant improvements in their mental health when treated with a moderate dose of EPA and DHA. This finding could ease the mind and, one hopes, encourage additional research.
Buydens-Branchey L, Branchey M, Hibbeln JR. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreased anger and anxiety in substance abusers. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:568-575. [PubMed]