Fatty acids and bipolar disorder

Abstract

Polyunsaturated fatty acids (FA) Include omega-3 and omega-6 FAs. These are broken down into short-and long-chain FAs. The short-chain FAs include the omega-3 FA alpha-linolenic acid (ALA) and the omega-6 FA linoleic acid (LA). The long-chain FAs include the omega-3 FAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) and the omega-6 FA arachadonic (AA) acid. The human body cannot make ALA and LA, so they are considered essential nutrients. Because only a limited supply of long-chain FAs can be formed in the body from short-chain FAs, the majority of long-chain FAs are derived from dietary sources and supplements.In this second of our series examining omega-3 and omega-6 FAs, we look at their effect on bipolar disorder.Bipolar disorderBipolar disorder, sometimes called manic-depression, is a chronic mood disorder affecting 2.8% of adults each year. It typically begins in late adolescence or early adulthood and continues throughout the lifespan, cycling between periods of depression, euthymia (normal mood), and mania. During periods of mania, people are easily distracted, need less sleep, are irritable or euphoric, and are hyperactive with racing thoughts and poor judgment. During the depressed phase, people often have low mood, loss of interest in pleasurable activities, changes in sleep or appetite, and decreased energy.It has been speculated that such increases in inflammation may increase neuronal cell damage and death. Therefore, it has been hypothesized that a shift in dietary intake to increase omega-3 and decrease omega-6 FAs would decrease secondary neuronal damage due to chronic inflammation.Epidemiologic studies support the link of altered concentrations of omega-3 FAs in bipolar disorder. Seafood consumption was inversely related to rates of bipolar disorder in one study. Some studies have reported lower concentrations of omega-3 FAs in patients being treated for bipolar disorder, although other studies have not replicated these findings.Omega-3 FA concentrations have been correlated with symptom severity in bipolar disorder. In one pediatric study, DHA concentrations were associated with depression severity, while EPA concentrations were more closely associated with manic symptoms. These results were replicated in a study of adults that found omega-3 FA concentrations and the omega-6:omega-3 FA ratio were associated with severity of manic symptoms.While early open-label studies of omega-3 FA supplementation for bipolar disorder were positive, results from more rigorous studies have been mixed. Three randomized controlled trials reported no benefit, while two reported improvements with omega-3 FAs supplementation in adults; however, two of the negative trials studied omega-3 FA supplementation in subpopulations (acute mania, women discontinuing mood stabilizers before becoming pregnant) , making it difficult to generalize the findings.Positive studies involved EPA or EPA and DHA, indicating that EPA supplementation is likely more important than DHA supplementation. Positive trials also reported significant improvement in depressive but not manic symptoms, suggesting that omega-3 FAs may play a limited role in adult bipolar disorder. The one randomized controlled in pediatric bipolar disorder reported no benefit of ALA supplementation.Given the disparity in methods, populations studied, and outcomes, it is difficult to draw any firm conclusions about the relationship between omega-3 and omega-6 FAs and bipolar disorder. While epidemiologic data indicate that there may be a relationship, it has not been supported in most clinical trials.What to tell patientsBipolar disorder is a serious illness that typically requires specialized psychiatric treatment and prescription medications. While epidemiologic data indicate that omega-3 and omega-6 FAs play a role in bipolar disorder, supplementation of FAs has not been shown effective as monotherapy for bipolar disorder. Studies indicate that any benefit is most likely applicable to the depressed phase of the illness.For patients wishing to augment their medication treatment, marine-derived omega-3 FAs (DHA, EPA) are preferred. Dosages in studies varied, but positive studies reported 2-4 g/d of EPA alone or in combination with DHA may be beneficial in adults for the depressive phase of the illness when no drug interactions or contraindications exist.Contributing writerAnne L. Hume, PharmD, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA’s Handbook of Nonprescription Drugs. Polyunsaturated fatty acids (FA) Include omega-3 and omega-6 FAs. These are broken down into short-and long-chain FAs. The short-chain FAs include the omega-3 FA alpha-linolenic acid (ALA) and the omega-6 FA linoleic acid (LA). The long-chain FAs include the omega-3 FAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) and the omega-6 FA arachadonic (AA) acid. The human body cannot make ALA and LA, so they are considered essential nutrients. Because only a limited supply of long-chain FAs can be formed in the body from short-chain FAs, the majority of long-chain FAs are derived from dietary sources and supplements. In this second of our series examining omega-3 and omega-6 FAs, we look at their effect on bipolar disorder. Bipolar disorderBipolar disorder, sometimes called manic-depression, is a chronic mood disorder affecting 2.8% of adults each year. It typically begins in late adolescence or early adulthood and continues throughout the lifespan, cycling between periods of depression, euthymia (normal mood), and mania. During periods of mania, people are easily distracted, need less sleep, are irritable or euphoric, and are hyperactive with racing thoughts and poor judgment. During the depressed phase, people often have low mood, loss of interest in pleasurable activities, changes in sleep or appetite, and decreased energy.It has been speculated that such increases in inflammation may increase neuronal cell damage and death. Therefore, it has been hypothesized that a shift in dietary intake to increase omega-3 and decrease omega-6 FAs would decrease secondary neuronal damage due to chronic inflammation.Epidemiologic studies support the link of altered concentrations of omega-3 FAs in bipolar disorder. Seafood consumption was inversely related to rates of bipolar disorder in one study. Some studies have reported lower concentrations of omega-3 FAs in patients being treated for bipolar disorder, although other studies have not replicated these findings.Omega-3 FA concentrations have been correlated with symptom severity in bipolar disorder. In one pediatric study, DHA concentrations were associated with depression severity, while EPA concentrations were more closely associated with manic symptoms. These results were replicated in a study of adults that found omega-3 FA concentrations and the omega-6:omega-3 FA ratio were associated with severity of manic symptoms.While early open-label studies of omega-3 FA supplementation for bipolar disorder were positive, results from more rigorous studies have been mixed. Three randomized controlled trials reported no benefit, while two reported improvements with omega-3 FAs supplementation in adults; however, two of the negative trials studied omega-3 FA supplementation in subpopulations (acute mania, women discontinuing mood stabilizers before becoming pregnant) , making it difficult to generalize the findings.Positive studies involved EPA or EPA and DHA, indicating that EPA supplementation is likely more important than DHA supplementation. Positive trials also reported significant improvement in depressive but not manic symptoms, suggesting that omega-3 FAs may play a limited role in adult bipolar disorder. The one randomized controlled in pediatric bipolar disorder reported no benefit of ALA supplementation.Given the disparity in methods, populations studied, and outcomes, it is difficult to draw any firm conclusions about the relationship between omega-3 and omega-6 FAs and bipolar disorder. While epidemiologic data indicate that there may be a relationship, it has not been supported in most clinical trials. Bipolar disorder, sometimes called manic-depression, is a chronic mood disorder affecting 2.8% of adults each year. It typically begins in late adolescence or early adulthood and continues throughout the lifespan, cycling between periods of depression, euthymia (normal mood), and mania. During periods of mania, people are easily distracted, need less sleep, are irritable or euphoric, and are hyperactive with racing thoughts and poor judgment. During the depressed phase, people often have low mood, loss of interest in pleasurable activities, changes in sleep or appetite, and decreased energy. It has been speculated that such increases in inflammation may increase neuronal cell damage and death. Therefore, it has been hypothesized that a shift in dietary intake to increase omega-3 and decrease omega-6 FAs would decrease secondary neuronal damage due to chronic inflammation. Epidemiologic studies support the link of altered concentrations of omega-3 FAs in bipolar disorder. Seafood consumption was inversely related to rates of bipolar disorder in one study. Some studies have reported lower concentrations of omega-3 FAs in patients being treated for bipolar disorder, although other studies have not replicated these findings. Omega-3 FA concentrations have been correlated with symptom severity in bipolar disorder. In one pediatric study, DHA concentrations were associated with depression severity, while EPA concentrations were more closely associated with manic symptoms. These results were replicated in a study of adults that found omega-3 FA concentrations and the omega-6:omega-3 FA ratio were associated with severity of manic symptoms. While early open-label studies of omega-3 FA supplementation for bipolar disorder were positive, results from more rigorous studies have been mixed. Three randomized controlled trials reported no benefit, while two reported improvements with omega-3 FAs supplementation in adults; however, two of the negative trials studied omega-3 FA supplementation in subpopulations (acute mania, women discontinuing mood stabilizers before becoming pregnant) , making it difficult to generalize the findings. Positive studies involved EPA or EPA and DHA, indicating that EPA supplementation is likely more important than DHA supplementation. Positive trials also reported significant improvement in depressive but not manic symptoms, suggesting that omega-3 FAs may play a limited role in adult bipolar disorder. The one randomized controlled in pediatric bipolar disorder reported no benefit of ALA supplementation. Given the disparity in methods, populations studied, and outcomes, it is difficult to draw any firm conclusions about the relationship between omega-3 and omega-6 FAs and bipolar disorder. While epidemiologic data indicate that there may be a relationship, it has not been supported in most clinical trials. What to tell patientsBipolar disorder is a serious illness that typically requires specialized psychiatric treatment and prescription medications. While epidemiologic data indicate that omega-3 and omega-6 FAs play a role in bipolar disorder, supplementation of FAs has not been shown effective as monotherapy for bipolar disorder. Studies indicate that any benefit is most likely applicable to the depressed phase of the illness.For patients wishing to augment their medication treatment, marine-derived omega-3 FAs (DHA, EPA) are preferred. Dosages in studies varied, but positive studies reported 2-4 g/d of EPA alone or in combination with DHA may be beneficial in adults for the depressive phase of the illness when no drug interactions or contraindications exist.Contributing writerAnne L. Hume, PharmD, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA’s Handbook of Nonprescription Drugs. Bipolar disorder is a serious illness that typically requires specialized psychiatric treatment and prescription medications. While epidemiologic data indicate that omega-3 and omega-6 FAs play a role in bipolar disorder, supplementation of FAs has not been shown effective as monotherapy for bipolar disorder. Studies indicate that any benefit is most likely applicable to the depressed phase of the illness. For patients wishing to augment their medication treatment, marine-derived omega-3 FAs (DHA, EPA) are preferred. Dosages in studies varied, but positive studies reported 2-4 g/d of EPA alone or in combination with DHA may be beneficial in adults for the depressive phase of the illness when no drug interactions or contraindications exist.Contributing writerAnne L. Hume, PharmD, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA’s Handbook of Nonprescription Drugs. Anne L. Hume, PharmD, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA’s Handbook of Nonprescription Drugs. Anne L. Hume, PharmD, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA’s Handbook of Nonprescription Drugs.