Joseph R. Hibbeln

Fish consumption and major depression

Sir—WHO estimates that major depression is the greatest single cause of disability worldwide. The annual prevalence of major depression shows nearly a 60-fold variation across countries, in a pattern similar to crossnational differences in mortality from coronary artery disease, which suggest that similar dietary risk factors could be important. Among healthy volunteers, low plasma concentrations of an essential fatty acid found in fish, docosahexaenoic acid, predict low concentrations of a marker of brain serotonin turnover, cerebrospinal fluid 5-hydroxyindolacetic acid (CSF 5HIAA). The finding that low concentrations of CSF 5-HIAA are strongly associated with depression and suicide have been widely replicated. Since docosahexaenoic acid is selectively concentrated in neural tissues and important for nervoussystem function, we tested the hypothesis that a high consumption of fish could be correlated with a lower annual prevalence of major depression (figure). The cross-national comparisons of the prevalence of major depression reported by Weissman and colleagues are among the most reliable crossnational data available. The rigorous methodologies used in these studies— large sample size (35 000), random prospective design, repeat sampling techniques, multiple community sampling, and use of a structured clinical interview with uniform internationally accepted diagnostic criteria—create confidence in the validity and comparability of these data. The structured interviews were independently verified as culturally appropriate for each community. The core biological symptoms that define major depression were the main factors used to determine the differences in prevalence of major depression across countries, rather than mood ratings which are prone to cultural bias. The economic data on apparent fish consumption was calculated by fish catch plus imports minus exports and are not as reliable as data from direct dietary surveys or tissue analyses, but do provide a comparable estimate across countries. The data on the annual prevalence of major depression reported by the Ministry of Welfare in Japan included 130 000 individuals, but did not use structured instruments for diagnosis or randomised population-sampling methods. However, exclusion of these Japanese data did not significantly affect the correlation analysis (r=0·77, p<0·03). The direction and power of the correlation between apparent fish consumption and major depression accords with recent clinical reports of individuals that higher concentrations of docosahexaenoic acid in red-bloodcell membranes (r= 0·80, p<0·01), as well as higher ratios of eicosapentaenoic acid to arachidonic acid in plasma (r= 0·73, p<0·01), predict less severe symptoms of depression. This correlation between apparent fish consumption and lower annual prevalence of major depression does not show that fish consumption can cause differences in the prevalence of major depression or that eating fish or fish oils are useful in treatment. Various cultural, economic, social, and other factors can confound this simple correlational relation.

Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century

BACKGROUND The consumption of omega-3 (n-3) and omega-6 (n-6) essential fatty acids in Western diets is thought to have changed markedly during the 20th century. OBJECTIVE We sought to quantify changes in the apparent consumption of essential fatty acids in the United States from 1909 to 1999. DESIGN We calculated the estimated per capita consumption of food commodities and availability of essential fatty acids from 373 food commodities by using economic disappearance data for each year from 1909 to 1999. Nutrient compositions for 1909 were modeled by using current foods (1909-C) and foods produced by traditional early 20th century practices (1909-T). RESULTS The estimated per capita consumption of soybean oil increased >1000-fold from 1909 to 1999. The availability of linoleic acid (LA) increased from 2.79% to 7.21% of energy (P < 0.000001), whereas the availability of α-linolenic acid (ALA) increased from 0.39% to 0.72% of energy by using 1909-C modeling. By using 1909-T modeling, LA was 2.23% of energy, and ALA was 0.35% of energy. The ratio of LA to ALA increased from 6.4 in 1909 to 10.0 in 1999. The 1909-T but not the 1909-C data showed substantial declines in dietary availability (percentage of energy) of n-6 arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Predicted net effects of these dietary changes included declines in tissue n--3 highly unsaturated fatty acid status (36.81%, 1909-T; 31.28%, 1909-C; 22.95%, 1999) and declines in the estimated omega-3 index (8.28, 1909-T; 6.51, 1909-C; 3.84, 1999). CONCLUSION The apparent increased consumption of LA, which was primarily from soybean oil, has likely decreased tissue concentrations of EPA and DHA during the 20th century.

Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: Evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis

Objective To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death. Design Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data. Setting Ambulatory, coronary care clinic in Sydney, Australia. Participants 458 men aged 30-59 years with a recent coronary event. Interventions Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups. Outcome measures All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group. Results The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07). Conclusions Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats. Trial registration Clinical trials NCT01621087.

Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia

Recent research suggests that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia. We review available clinical research on abnormalities in membrane fatty acid composition and metabolism in schizophrenia, and therapeutic trials of fatty acid in this disorder. All potentially relevant English-language articles were identified from the medical and psychiatric literature with the aid of computer searches using key words such as lipids, phospholipids, prostaglandins and schizophrenia. All studies which include human subjects are reviewed. Empirical studies related to membrane hypotheses of schizophrenia focus on: 1) assessment of prostaglandins (PG) and their essential fatty acid (EFA) precursors in the tissues of patients with schizophrenia; 2) evaluation of the niacin flush test as a possible diagnostic marker; 3) evaluation of phospholipase enzyme activity; 4) NMR spectroscopy studies of brain phospholipid metabolism; and 5) therapeutic trials of PG precursors for the treatment of schizophrenia. The most consistent clinical findings include red blood cell fatty acid membrane abnormalities, NMR spectroscopy evidence of increased phospholipid turnover and a therapeutic effect of omega-3 fatty acid supplementation of neuroleptic treatment in some schizophrenia patients. Studies of EFA metabolism have proved fruitful for generating and testing novel etiologic hypotheses and new therapeutic agents for schizophrenia. Greater attention to factors that influence tissue EFA levels such as diet, tobacco and alcohol are required to reconcile inconsistent findings. Treatment studies, although promising, require independent replication.

Obesity Among Those with Mental Disorders: A National Institute of Mental Health Meeting Report

The National Institute of Mental Health convened a meeting in October 2005 to review the literature on obesity, nutrition, and physical activity among those with mental disorders. The findings of this meeting and subsequent update of the literature review are summarized here. Levels of obesity are higher in those with schizophrenia and depression, as is mortality from obesity-related conditions such as coronary heart disease. Medication side effects, particularly the metabolic side effects of antipsychotic medications, contribute to the high levels of obesity in those with schizophrenia, but increased obesity and visceral adiposity have been found in some but not all samples of drug-naïve patients as well. Many of the weight-management strategies used in the general population may be applicable to those with mental disorders, but little is known about the effects of these strategies on this patient population or how these strategies may need to be adapted for the unique needs of those with mental disorders. The minimal research on weight-management programs for those with mental disorders indicates that meaningful changes in dietary intake and physical activity are possible. Physical activity is an important component of any weight-management program, particularly for those with depression, for which a substantial body of research indicates both mental and physical health benefits. Obesity among those with mental disorders has not received adequate research attention, and empirically-based interventions to address the increasing prevalence of obesity and risk of cardiovascular and metabolic diseases in this population are lacking.

Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression

Objective:  Postpartum depression (PPD) affects 10–15% of mothers. Omega‐3 fatty acids are an intriguing potential treatment for PPD.

Omega-3 fatty acids and supportive psychotherapy for perinatal depression: A randomized placebo-controlled study

BACKGROUND Perinatal major depressive disorder (MDD), including antenatal and postpartum depression, is common and has serious consequences. This study was designed to investigate the feasibility, safety, and efficacy of omega-3 fatty acids for perinatal depression in addition to supportive psychotherapy. METHODS Perinatal women with MDD were randomized to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), 1.9g/day, or placebo for 8weeks. A manualized supportive psychotherapy was provided to all subjects. Symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D) and Edinburgh Postnatal Depression Scale (EPDS) biweekly. RESULTS Fifty-nine women enrolled; N = 51 had two data collection points that allowed for evaluation of efficacy. Omega-3 fatty acids were well tolerated. Participants in both groups experienced significant decreases in EPDS and HAM-D scores (p<.0001) from baseline. We did not find a benefit of omega-3 fatty acids over placebo. Dietary omega-3 fatty acid intake was low among participants. LIMITATIONS The ability to detect an effect of omega-3 fatty acids may have been limited by sample size, study length, or dose. The benefits of supportive psychotherapy may have limited the ability to detect an effect of omega-3 fatty acids. CONCLUSIONS There was no significant difference between omega-3 fatty acids and placebo in this study in which all participants received supportive psychotherapy. The manualized supportive psychotherapy warrants further study. The low intake of dietary omega-3 fatty acids among participants is of concern, in consideration of the widely established health advantages in utero and in infants.

Dietary Linoleic Acid Elevates Endogenous 2‐AG and Anandamide and Induces Obesity

Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2‐arachidonoylglycerol (2‐AG) and anandamide (AEA) is the ω‐6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. LA was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the United States during the 20th century. Mice were fed diets containing 1 en% LA, 8 en% LA, and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium‐fat diets (35 en% fat) and high‐fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA‐phospholipids (PL) in liver and erythrocytes, tripled 2‐AG + 1‐AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA‐PL by adding 1 en% long‐chain ω‐3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2‐AG + 1‐AG and AEA resulting in the development of diet‐induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA‐PL pool and normalize endocannabinoid tone.

Omega-3 Polyunsaturated Essential Fatty Acid Status as a Predictor of Future Suicide Risk

OBJECTIVE Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behavior. Predicting risk of future suicidal behaviors by essential fatty acid status merits examination. METHOD Plasma polyunsaturated fatty acid levels in phospholipids were measured in 33 medication-free depressed subjects monitored for suicide attempt over a 2-year period. Survival analysis examined the association of plasma polyunsaturated fatty acid status and pathological outcome. RESULTS Seven subjects attempted suicide on follow-up. A lower docosahexaenoic acid percentage of total plasma polyunsaturated fatty acids and a higher omega-6/omega-3 ratio predicted suicide attempt. CONCLUSIONS A low docosahexaenoic acid percentage and low omega-3 proportions of lipid profile predicted risk of suicidal behavior among depressed patients over the 2-year period. If confirmed, this finding would have implications for the neurobiology of suicide and reduction of suicide risk.

Nutritional medicine as mainstream in psychiatry

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.