Lipids (fats) account for approximately 60% of the brain's dry weight. These lipids are important for normal brain function. Increasing amounts of data demonstrate that abnormal lipid content is common in brain disorders such as Alzheimer's Dementia (AD) and mental depression. As much as 20 per cent of the fat in the brain is the omega-3 DHA. DHA is present in relatively large amounts in brain tissue, significantly more than in other tissues or organs.
Polyunsaturated fatty acids (PUFAs) provide the brain cells with a unique degree of elasticity and fluid binding capacity. The most important PUFAs in the brain are docosahexaenoic acid (DHA) and arachidonic acid (ARA). These are the fatty acids of the omega-3 and omega-6 series with the highest number of double bonds. It is not fully known why the brain requires these PUFAs specifically, but increasing data documents the fact that the action of DHA and ARA are essential for a series of brain functions such as the fine-tuning of mood, sleep/alertness, memory and emotions.
In the unborn child, brain maturation takes place mainly during the last three months of pregnancy. During this interval the fetus accumulates large amounts of DHA and ARA. These PUFAs are taken from the placenta circulation of the mother, and so the mother's diet has to be rich in DHA through seafood or omega-3 supplements..
After birth, the brain of the newborn continues to accumulate omega-3s, and mother's milk contains omega-3 fatty acids including EPA and DHA. The relative percentages will be high if the mother has a sufficient dietary intake of fish or fish oil supplements. However, many mothers do not breastfeed their babies. Most infant formulas do not contain omega-3 fatty acids, which may lead to unsatisfactory quantities of this essential fatty acid in the child’s brain.
Children given infant formulas containing omega-3 fatty acids usually develop visual acuity and intellectual functions better than those given standard formulas. In the retina of the eye we find the body’s highest concentration of DHA, where it is directly engaged in the transformation of light energy into electric energy that later is conducted through the visual nerve to the posterior part of the brain. Studies have shown a statistically significant improvement in visual acuity and problem solving capacity in children given omega-3 compared to those given infant formulas that did not contain omega-3.
Omega-3s and mental disorders
Mental depression is very common, affecting 8-10% of the population at any time. Statistics show that the prevalence of major depression has increased and the age of onset has decreased in every decade during the 21st century in the Western World. As a result, anti-depressive medications are the most common prescription written in many countries.
In fact, patients with major depression usually have low levels of omega-3 fatty acids in their blood analysis.
A dietary survey of 9 countries around the world clearly demonstrated a higher prevalence of mental depression in populations not eating fish.(1) In a recently published article, US scientists found low contents of omega-3 fatty acids in mothers milk of women with depressive disease after delivery. Mothers without depression had significantly different values.(2) People in Iceland do not experience seasonal winter depression as commonly as in Canada, possibly due to the very different habits of seafood intake.(3) People in Finland with a relatively frequent intake of fish have less frequent depression and significantly lower risk of suicide compared to those not eating fish.(4) Patients with severe depression have, in general, low levels of omega-3 fatty acids in the blood.(5)
Marine omega-3 fatty acids could be important for the prevention and even treatment of depression.
Supplementation with omega-3 fatty acids and antioxidants improves schizophrenia
Reduced levels of membrane essential fatty acids, namely arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DHA), and their association with psychopathology have been consistently reported in both chronically medicated as well as never-medicated schizophrenic patients.
In this study 33 schizophrenic patients were supplemented with a mixture of EPA/DHA (180:120 mg) and antioxidants (vitamin E/C, 400 IU:500 mg) orally morning and evening for 4 months.(6) Physiological and clinical measures were carried out at pre-treatment, post-treatment, and after 4 months of a post-supplementation period to determine the stability of treatment effects within patients.
There was a significant reduction in psychopathology based on specific tests (BPRS, PANSS, QOL). The supplemented fatty acid levels returned to pre-treatment levels after 4 months of supplementation washout. However, the clinical improvement was significantly retained.
This study establishes that fatty acid supplementation is an effective treatment to improve the outcome of schizophrenia.
- Hibbeln JR. Fish consumption and major depression. The Lancet 1998; 351:1213-1215
- Hibbeln JR. Seafood consumption, the DHA content of mother's milk and prevalence rates of postpartum depression: a cross-national, ecological analysis.
J Affective Disorders 2002; 69:15-29
- Magnusson A, et al. Lack of seasonal mood change in the Islandic population: results of a cross-sectional study. Am J Psychiatry 2000; 157:234-238
- Tanskanen A,et al. Fish consumption and depressive symptoms in the general population in Finland. Psychiatric Services 2001; 52:529-531
- Maes M, et al. Fatty acid composition in major depression. J Affective Disorders 1996; 38:35-46
- Schizophrenia Research, 62(3): 195-204, 2003
The Brain's Omega-3 Paradox
The omega-3 DHA is highly concentrated in the cerebral cortex and is the building block of human brain tissue. The brain is made up of 60% fatty tissue, and in that fatty tissue approximately 30% of the structural lipid fat in the neurons is comprised of DHA. DHA is also abundant in the gray matter of the brain and aids in the communication between cells. Interestingly however, while the omega-3 EPA is richly present in other cells, the brain has only sparse amounts.
Despite these facts, recent research indicates that EPA has positive effects in the treatment of major depressive conditions, while DHA does not. And supplementation with DHA does not necessarily correct a DHA deficiency in the brain, whereas supplementation with EPA does.
Analysis of the omega-3 content of red blood cells has shown that depressive patients have a significantly lower content of EPA and DHA compared to normal control patients.(1) There have been three published controlled clinical studies to examine the effects of treatment with marine omega-3 fatty acids on patients with depressive diseases:
- A Boston study of manic depressive patients in remission on their habitual treatment clearly demonstrated that those given omega-3 fatty acids EPA and DHA in combination stayed in remission significantly better than those given placebo.(2)
- In a study from Israel of patients with major depressive disease, those given EPA alone showed significantly improved mental status while those given placebo showed no effect. (3)
- A recent UK study examined the anti-depressive effect of DHA alone in depressive patients. However, the effect of DHA treatment was not different from the placebo treated group. (4)
So it seems that either EPA alone, or the natural combination of EPA and DHA as found in fish oil, is responsible for anti-depressive effects.
As the brain contains high amounts of DHA but almost no EPA, one would expect more positive effects from DHA supplementation. However these fatty acids may trigger different actions in the brain. DHA has important effects providing mechanical and functional properties in brain cell membranes. EPA on the other hand is an important precursor for local acting hormones, the eicosanoids, known to have psychotropic effects.
As for the other part of the paradox, DHA deficiency in the brain can be caused by the over activity of an enzyme (cPLA2) which breaks DHA molecules away from the brain cells. (5,6) Researchers have noted this action in patients with various brain and cognitive disorders. PLA2 activity correlates to oxidative stress in the brain – the stronger the oxidative stress, the higher the PLA2 activity. However the omega-3 fatty acid EPA is a PLA2 inhibitor, providing support in eliminating this source of DHA degeneration. (Finnen and Lovell 1991, Ho et al 2000)
Results from ongoing studies will probably shed further light on the omega-3 fatty acid combination most effective for brain function. However, marine omega-3 fatty acids with EPA and DHA in the natural combination are a good starting point for prevention of depression and the maintenance of good mental health.
- Maes M, et al. “Fatty acid composition in major depression.” J Affective Disorders 1996; 38:35-46
- Stoll AL, et al. “Omega-3 fatty acids in bipolar disorder.” Arch Gen Psychiatry 1999; 56:407-412
- Nemets B, et al. “Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder.” Am J Psychiatry 2002; 159:477-479
- Marangell LB, et al. “A double blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression.” Am J Psychiatry 2003; 160:996-998
- Farooqu A. et al. “Plasmalogens, phospholipase A2, and docosahexaenoic acid turnover in brain tissue.” J Mol Neurosci 2001; 16:263-272.
- Gattaz W. et al. “Increased platelet phospholipase A2 activity in schizophrenia.” Schizophrenia Research 1995; 16:1-6.A
Omega-3 and Alzheimer's Dementia
Brains of patients with dementia contain low concentrations of DHA
Alzheimer’s Dementia (AD) is uncommon before the age of 70, but with increasing longevity this constitutes an increasing problem for the individual, the family, and society. The human brain contains tissues which can convert ALA and LA (the precursors) to DHA and ARA. In normal individuals, analysis of fatty acids reveals only trace amounts of those precursors and large amounts of DHA and ARA. However, in patients with dementia or AD this is very different. Brain tissue from these patients has an unusually high content of ALA and LA and a low concentration of DHA.
DHA supplementation significantly decreases risk of Alzheimer’s
A study from the University of Guelph found that Alzheimer's patients and elderly patients with various types of dementia all had lower levels of the omega-3 DHA (docosahexaenoic acid) than did subjects with normal cognitive functioning.
Lead researcher Julie Conquer, director of the University’s Human Nutraceutical Research Unit said, "Low DHA levels are already affiliated with several disorders. Given that our research indicates that decreased levels of DHA also appear to accompany cognitive impairment with aging, we think this is a sign we should all be eating more fish".
In a recent Tufts University study, researchers analyzed ten years of data taken from more than 1,100 elderly men and women who had participated in the Framingham Heart Study. Results showed that those who had high levels of DHA and who also ate about three fish meals each week had a nearly 50% reduced risk of developing Alzheimer’s Disease.
Although these studies demonstrate that DHA appears to help prevent Alzheimer's disease, they don't demonstrate a clear cause and effect. However, new research from the University of California Los Angeles (UCLA) provides that link.
Amyloids are proteins that collect in strands of waxy fibers in the brain, and are believed to be responsible for Alzheimer's disease. Amyloid precursor protein (APP) is a protein that prompts the production of the amyloid fibrils. To assess the effect of dietary DHA on the processing of APP, the UCLA scientists divided mice into three groups. The groups received either a high-DHA diet, a low-DHA diet, or a DHA-free diet.
When the UCLA team later analyzed brain tissue samples, they found that total amyloid accumulation was more than 70% less in mice that received a high-DHA diet compared to those in the DHA-free group, and was significantly less than those in the low-DHA group.
"This study is significant because it shows that DHA added to the diet altered the processing of the amyloid precursor protein and the accumulation of its toxic amyloid protein metabolite that is widely believed to cause Alzheimer's. These and other beneficial results were observed even when the diets were changed late in life," said Dr. Greg Cole, the study's lead investigator.
These studies show the critical importance of DHA in avoiding the onset of Alzheimer’s Disease.
The Rotterdam Study
About 2.5 million people in the US suffer from advanced AD and the number is increasing. In countries with a high fish intake these figures are different. In Norway and Japan AD is less common. In the Rotterdam Study in Holland, about 5,500 healthy individuals were investigated regarding dietary and smoking habits, and given laboratory tests and cognition tests to reveal early dementia. This was repeated after about two years, and during that time about 2% of the participants had developed AD. The data clearly demonstrated that risk factors for development of AD included a high intake of saturated fat and cholesterol, and smoking. The data also showed that regular consumption of fish.seemed to prevent the development of AD.
Nakada T et al. Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease. Neuroreport 1990; 1(2):153-155
Conquer, Julie A. et al. “Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.” Lipids, Vol. 35, December 2000, pp. 1305-12
Cole G. et al. "A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model" The Journal of Neuroscience, Vol. 25, No. 12, March 2005
Kalmijn S et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann of Neurol 1997;42(5):776-782
Martinez M. Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis. Versicherungsmedizin 1996;31 Suppl:145-152