Research shows benefit for mentally healthy people and substance abusers alike; animal study suggests omega-3s help ensure the brain’s fuel supply
by Craig Weatherby
If you're reasonably happy, but want to feel even better about life, you may want to eat more fish and take fish oil. And if you're angry too much of the time, or feel as though your brain is running on empty, the same advice may apply.
This week, we present summaries of three recent research reports about the effects of omega-3s on mental health and performance.
Study #1: Marine Omega-3s May Help Make People Happy
Taken together, research results published over the past decade demonstrate that diets lacking in the marine omega-3 fatty acids from fish can have negative impacts on mental health.
Omega-3 deficiencies appear to promote and exacerbate common psychological conditions, including depression, bipolar (manic/depressive) disorder, schizophrenia, and attention deficit disorder.
The results of two studies published late last year were the first to demonstrate the positive effects of marine
omega-3s on brain performance in adults (see “Moderate Fish Intake Boosts Brain Power through Middle Age and Beyond” and “Omega-3s Enhance Mood and Brain Speed”).
But until recently, no one had examined the psychological effects of supplemental omega-3s in healthy people.
Last year, a team of researchers from the University of Pittsburgh and Brown University set out to fill this knowledge gap, and they presented their results earlier this month at the 64th annual meeting of the American Psychosomatic Society in Denver (Conklin SM 2006).
The team included Cmdr Joseph Hibbeln, M.D. of the National Institutes of Health, a pioneer of the study of marine omega-3s in mental health, who we met and spoke with at last year’s Seafood & Health conference.
The new study was designed to discover any connection between people’s blood levels of omega-3s and their overall mood and attitude toward life.
The researchers recruited 106 middle-aged men and women who had high cholesterol levels but were otherwise healthy. None took fish oil supplements or any psychotropic (mind-affecting) drugs.
All of the participants provided blood samples, and took standard tests designed to gauge a person’s relative degree of depression, impulsivity, and agreeableness.
The results showed that participants with lower blood levels of omega-3 fatty acids (EPA and DHA) were most likely to display mild or moderate symptoms of depression, a more negative, disagreeable outlook, and less impulse control.
In contrast, the study participants with higher blood levels of omega-3s were less likely to display any symptoms of depression, and to exhibit a positive, agreeable outlook and better impulse control.
The research team came to this conclusion: "In conjunction with published research, these data suggest that dietary intake of omega-3 fatty acids may be a determinant ... in affect [mood] regulation, impulse control and personality.”
In other words, it appears that diets high in omega-3s help healthy people to feel happier and more agreeable, and leave them less prone to conflict or depression.
Study 2: Marine Omega-3s Ameliorate Anger in Substance Abusers
The positive results of a small, placebo-controlled clinical trial released late last year hold out hope that marine omega-3 supplements may alleviate chronic anger among substance abusers. Chronic anger can lead to aggressive behavior, so anything that reduces these feelings may help reduce hostility and violence.
These encouraging findings came as no surprise to people familiar with evidence from prior studies. Over the past decade, research has shown that diets low in marine omega-3s yield higher rates of depression and violence.
In the current study, researchers recruited 24 patients in a Veteran’s Administration outpatient treatment program for people with a history of substance abuse, some of whom had displayed aggressive behavior.
The substance-abuse patients were divided into two groups:
- Thirteen took daily fish-oil capsules containing 3 grams of omega-3s.
- Eleven took similar-looking placebo capsules daily, which contained standard vegetable oils low in omega-3s and high in omega-6s.
Neither the researchers nor the patients knew which group was which (i.e., this study employed a desirable “double-blind” design).
Four of the 13 patients in the fish-oil group and 4 of the 11 patients in the placebo group had a history of assaults and seven patients in each group had been jailed for offences ranging from drug possession to theft, DWI, weapon possession, and assaults
The trial lasted 3 months, and the participants took a mood-defining questionnaire (modified version of the Profiles of Mood States test) at the outset and every month thereafter.
In addition, six patients in the fish-oil group and 8 patients in the placebo group took the same test once during each of three additional months.
Unlike the 11 patients who received placebos, the 13 patients who received fish-oil capsules showed a progressive decline in anger scores.
The 6 patients in the fish oil group who were followed for an additional three months (i.e., after stopping the fish oil) showed a progressive increase in anger scores from the 4th to the 6th month, but their scores did not return to the high anger levels seen at the outset.
No such positive trend was seen in the 8 patients who received placebo capsules.
As the authors concluded,
- “… daily administration of 3 grams of n-3 PUFAs for a period of 3 months significantly decreased feelings of anger in a population of substance abusers by comparison with the administration of a placebo. … “
- “These data give support to epidemiological [population] studies showing a decrease in homicides in countries where the consumption of foods rich in n-3 PUFAs such as fish is high. …”
- “Supplements of n-3 [omega-3] PUFAS, [which] are both inexpensive and well tolerated, might be considered as treatment adjuncts in patients displaying these behaviors.”
We can only hope that these results, and those of prior studies, will be used to enhance treatment of people addicted to alcohol or drugs, especially since prior research supports the value of omega-3s in mood control.
In one of the first such investigations (Hibbeln JR 1998), low levels of omega-3s correlated closely with low levels of the neurotransmitters dopamine and serotonin—serotonin deficiency being a known risk factor for depression and suicide—and that these deficiencies were significantly greater in alcoholics.
A later study showed that among hospitalized cocaine addicts (Buydens-Branchey L 2003), the most aggressive patients had significantly lower levels of omega-3s.
And the findings of another study co-authored by Dr. Hibbeln (Iribarren C 2004) showed that inner-city teens with higher intake of fish and the omega-3 fatty acid called DHA enjoyed lower levels of hostility.
As his team concluded, “These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 [omega-3] fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 [omega-3] fatty acids and hostile personality merits further research.”
Study 3: Omega-3 Shortage May Cut Brain’s Sugary Fuel Supply
The membranes of human and animal brain cells consist largely of two long-chain fatty acids: omega-3 DHA (docosahexaenoic acid) and omega-6 ARA (arachidonic acid). This is why DHA is required for optimum retina and brain development and function, and it explains why dietary deficiencies of DHA impair learning and promote depression and attention-deficit disorders.
Now, in addition to its critical structural and functional role in brain cell membranes, the results of new research confirm that omega-3 DHA is needed to maintain the metabolic system that transports fuel to brain cells.
The brain’s primary fuel is the simple sugar known as glucose or “blood sugar”. And because the brain is highly vulnerable to damage from toxins, the tiny, specialized blood vessels that carry blood and nutrients into it permit entry only to harmless substances the brain needs, including glucose. This highly selective barricade is known as the blood-brain barrier.
Glucose crosses the blood-brain barrier hitched to a “transport protein” called GLUT1, and it reaches the brain’s astrocyte cells on the back of a slightly modified version (isoform) of GLUT1. The brain’s neuronal cells receive their glucose from a transport protein called GLUT3.
The results of a recently published study by French researchers indicate that rats raised on diets deficient in DHA suffer a 30 percent drop in the amount of glucose absorbed by brain cells (astrocytes and neurons) in three regions of the brain.
Investigators at France’s National Institute of Agricultural Research (INRA) performed their research in two groups of male rats:
- The “test” group was nursed by mothers that had been fed DHA-deficient diets starting two weeks prior to mating.
- The “control” group was nursed by mothers that had been fed a diet with ample amounts of DHA starting two weeks prior to mating.
Then, from weaning until three months of age, the pups in each group were fed the same diets their mothers’ received (i.e., either deficient or abundant in DHA).
Among the rats fed DHA-deficient diets, tissue levels of DHA were significantly decreased, while levels of its “emergency replacement”—the omega-6 version of a fatty acid called DPA (docosapentaenoic acid)—rose significantly.
At the same time, the chemical activity of both forms of the GLUT1 transporter protein was reduced substantially in the DHA-deficient rats, compared with the control animals: GLUT1 activity dropped by 25 percent in the rats’ blood brain barriers—thus reducing the brain’s supply of glucose by 25 percent—while activity of the astrocyte-supplier form of GLUT1 dropped by 30 percent, thereby starving that particular group of brain cells even further.
The activity of GLUT3, which carries glucose to neuronal cells, was unaffected by dietary DHA deficiency. However, since the amount of glucose crossing the blood-brain barrier was reduced, the amount of glucose available for the GLUT3 protein to transport to neurons was also reduced.
These findings mean that a dietary deficiency of DHA can impair brain function in two ways. The first effect was known already, while the second negative impact was revealed by the French team’s groundbreaking research:
- Reduce the functional efficiency of cell membranes.
- Starve brain cells of glucose, their primary fuel.
In other words, the body needs ample amounts of marine omega-3s to keep sugary fuel flowing to brain cells, which makes fish (and fish oil) “brain food” in more ways than one.
Sources (Study 1)
- Conklin SM, Harris JI, Manuck SB, Hibbeln JR, Muldoon MF. Plasma fatty acids are associated with normative variation in mood, personality, and behavior. Abstract 1228, American Psychosomatic Society 64th Annual Meeting, March 1-4, 2006, Denver, Colorado. Accessed online March 10, 2006 at http://www.psychosomatic.org/events/AbstractsForJournal06.pdf.
- Hibbeln JR. Fish consumption and major depression (letter). Lancet 1998; 351: 1213.
- Hibbeln JR. Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: A cross-national, ecological analysis, Journal of Affective Disorders, accepted for publication.
- Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 2002: 159: 477-479.
- Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002: 59: 913-919.
- Sampalis F, Bunea R, Pelland MF, et al. Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea. Altern Med Rev 2003;8: 171-179.
- Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder; a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999: 407-412.
- Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Vilnamaki H, Lehtonen J, Vartiainen E. Fish consumption and depressive symptoms in the general population of Finland. Psychiatric Serv 2001: 52:529-31.
Sources (Study 2)
- Buydens L, Branchey M, Roy A. N-3 Polyunsaturated Fatty Acids Decrease Feelings of Anger in a Population of Substance Abusers. Neuropsychopharmacology. , 2005;30(1):S87-S88.
- Buydens-Branchey L, Branchey M, McMakin DL, Hibbeln JR. Polyunsaturated fatty acid status and aggression in cocaine addicts. Drug Alcohol Depend. 2003 Sep 10;71(3):319-23.
- Hibbeln JR. Seafood consumption and homicide mortality. A cross-national ecological analysis. World Rev Nutr Diet. 2001;88:41-6.
- Colin A, Reggers J, Castronovo V, Ansseau M. [Lipids, depression and suicide] Encephale. 2003 Jan-Feb;29(1):49-58. Review. French.
- Iribarren C, Markovitz JH, Jacobs DR, Schreiner PJ, Daviglus M, Hibbeln JR. Dietary intake of n-3, n-6 fatty acids and fish: Relationship with hostility in young adults-the CARDIA study. Eur J Clin Nutr. 2004 Jan; 58(1): 24-31.
- Virkkunen ME, Horroboin DF, Jenkins DK, Manku MS: Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent and impulsive offenders. Biol Psychiatry 1987; 22: 1087-1096.
- Hamazaki T, Sawazaki S, Itomura M, Asaoka E, Nagao Y, Nishimura N, Yazawa K, Kuwamori T, Kobayashi M: The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J Clin Invest 1996; 97: 1129-1133.
- Weidner G, Connor SL, Hollis JF, Connor WE: Improvements in hostility and depression in relation to dietary change and cholesterol lowering. Ann Int Med 1992; 117: 820-823.
- Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE, Vaughan MR, Rawlings R, Salem N Jr. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psychiatry. 1998 Aug 15;44(4):243-9.
- Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 1998; 44: 235-242.
- Hibbeln JR, Salem N Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clinical Nutr 1995; 62: 1-9.
- Hibbeln JR, Salem N Jr. Risks of cholesterol-lowering therapies. Biological Psychiatry 1996; 40: 7: 686-687.
- Hibbeln JR, Umhau JC, George DT, Salem N Jr. Do plasma polyunsaturates predict hostility and depression? World Rev Nutr Diet. 1997;82:175-86. Review.
- Tanskanen A, Hibbeln JR, Hintikka J, Haatainen K, Honkalampi K, Viinamaki H. Fish consumption, depression, and suicidality in a general population. Arch Gen Psychiatry. 2001 May;58(5):512-3. No abstract available.
- Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamaki H, Lehtonen J, Vartiainen E. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv. 2001 Apr;52(4):529-31.
- Hibbeln JR, Salem N Jr. Risks of cholesterol-lowering therapies. Biol Psychiatry. 1996 Oct 1;40(7):686-7.
- Cott J, Hibbeln JR. Lack of seasonal mood change in Icelanders. Am J Psychiatry. 2001 Feb;158(2):328.
Sources (Study 3)
- Pifferi F, Roux F, Langelier B, Alessandri JM, Vancassel S, Jouin M, Lavialle M, Guesnet P. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr 2005;135:2241-2246.
- Champeil-Potokar G, Denis I, Goustard-Langelier B, Alessandri JM, Guesnet P, Lavialle M. Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6 polyunsaturated fatty acid balance in their membrane phospholipids. J Neurosci Res. 2004 Jan 1;75(1):96-106.
- Zimmer L, Vancassel S, Cantagrel S, Breton P, Delamanche S, Guilloteau D, Durand G, Chalon S. The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr. 2002 Apr;75(4):662-7.
- Aas V, Rokling-Andersen MH, Kase ET, Thoresen GH, Rustan AC. Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells. J Lipid Res. 2006 Feb;47(2):366-74. Epub 2005 Nov 21.