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December 2003

Omega-3 Fatty Acids: Vital to a Longer, Healthier Life
By Dale Kiefer

Omega-3s and Neuropsychiatric Disorders
Evidence is mounting that after several generations of omega-3 deprivation, Americans’ overall health is deteriorating. Depression, suicide, violence, and formerly rare and mysterious disorders, such as autism, are becoming increasingly common. It is impossible to quantify the exact effects of a simple but profound change in the diet of an entire nation. But some scientists believe that a move away from a balanced ratio of omega-6 to omega-3 fatty acids, which began about a century ago, has affected us in ways we are only now beginning to comprehend. And the changes have been anything but positive.

Heart disease and cancer rank among our biggest killers. It is no coincidence that most Americans consume far too few omega-3s, nor is it a coincidence that omega-3 supplementation has been shown to improve cardiovascular health and to inhibit certain types of cancers.37-39,44 Is there a similar connection between simple diet and the rising incidence of disorders such as dyslexia, ADHD, depression, schizophrenia, and autism? Some scientists are convinced the answer is “yes.”

And speculation regarding omega-3s’ role in neurological health does not end there. Experiments have shown that supplementation with the omega-3 fatty acid DHA increases the frequency of a particular type of brain wave that is associated with memory and learning.42 Other studies have shown that infants receiving adequate omega-3s develop visual acuity sooner and perform better on intelligence tests than infants deprived of sufficient omega-3s.25-28 Omega-3s are supplied naturally in breast milk, provided the mother’s intake of omega-3s from plant or marine sources is adequate. But until recently, crucial omega-3s were absent from commercial infant formulas. Even now, omega-3s are only available in special, more expensive infant formulas.

Aversion to Fish May Be Depressing
For several years, researchers have noted a correlation between omega-3 deficits and severity of depression. Patients with the lowest levels of essential omega-3 fatty acids tend to be the most severely depressed, while healthy control subjects are more likely to have normal levels of omega-3s, as measured in red blood cell membranes.17 In a recently published clinical paper, researchers in the Netherlands reported that subjects with low levels of omega-3 fatty acids (and high omega-6 to omega-3 ratios) were significantly more likely to be depressed than those whose levels of omega-3s approached a more balanced level. The study group consisted of more than 3,000 adults over the age of 60, and inflammation and atherosclerosis were ruled out as confounding factors. The finding, researchers noted, “suggests a direct effect of fatty acid composition on mood.”15

The relationship between mood and fatty acid composition in the body also has been confirmed by research conducted in the U.S. by Andrew Stoll, M.D., Assistant Professor of Psychiatry at Harvard Medical School and director of the Psychopharmacology Research Laboratory at McLean Hospital in Belmont, MA. Dr. Stoll has focused his extensive research efforts on depression (including post-partum depression) and bipolar disorder (or manic-depressive illness). In numerous medical journal articles and in his book The Omega-3 Connection, Dr. Stoll has documented impressive results with omega-3 supplementation among patients ranging from those with treatment-resistant major depression to post-partum depression and bipolar disorder.16,18

Other researchers also have confirmed a definitive link between consumption of omega-3s and mental health. Studies have examined either blood or adipose tissue levels of omega-3s. They have consistently revealed a correlation between low levels of omega-3s and depression.12 Omega-3 supplementation has proven effective in the treatment of mild to moderate depression, or as an adjunct to therapy with modern drugs, especially in bipolar disorder. But there appears to be a point at which omega-3 supplementation is too little, too late. Supplementation appears to be largely ineffective in cases of major depression.19 One small but well-designed study found no significant benefit from treatment of major depression with DHA versus placebo.20 Even in these cases, however, omega-3 supplementation may provide a boost to standard therapy, particularly in treatment-resistant patients.21

As Dr. Stoll points out in The Omega-3 Connection, the link between omega-3s and heart health is well established and fairly well known among the general public. But research linking mood and omega-3s is relatively new, and much remains to be explored. Some studies provide indirect evidence of the importance of omega-3s to normal brain function, but definitive work remains to be done before scientists and the public are likely to embrace the notion that something as simple as changing dietary habits can affect so many lives, in so many ways, so profoundly.

The brain-health connection is hardly surprising, however—lipids are integral to the structure and function of the brain, which comprises about 60% lipids (fat). What is surprising is that brain-lipid abnormalities are only now receiving the close scrutiny they clearly deserve. The leukodystrophies, for instance, represent an entire class of neurological disorders caused by flaws in the fatty myelin sheath, which insulates a key component of nerve cells and allows propagation of nerve signals. Some scientists are suggesting that neuropsychiatric disorders such as dyspraxia (loss of coordination), autistic spectrum disorders, ADHD, schizophrenia, and dyslexia – which often have features that overlap one another – should be re-classified under the blanket term phospholipid spectrum disorders. This new term recognizes the underlying cellular lipid abnormalities that link these seemingly disparate yet related disorders.22

In essence, phospholipid spectrum disorders are characterized by abnormalities in the phospholipid and fatty acid composition of neural membranes. Cell membranes play a crucial role in controlling the flow of chemicals and nutrients trafficking between cells’ interiors and the outside. Cell membranes are largely composed of lipids, so any abnormalities in those lipids may cause interruptions in normal communication among neurons. Traditionally, scientists have sought to improve communication by focusing on the neurotransmitters, which carry messages from cell to cell. In the case of depression, for instance, it is believed that symptoms arise when the normal flow of serotonin, a powerful mood-regulating neurotransmitter, is interrupted.

Indeed, many groundbreaking therapies, including the new class of selective serotonin reuptake inhibitors (SSRIs), such as Prozac® and Zoloft®, have succeeded by enhancing the availability of one or more neurotransmitters. But the newer, phospholipid-spectrum-disorders approach revisits the problem by addressing underlying abnormalities in cell membranes. Because omega-3s fill an invaluable niche in cellular membrane architecture, it follows that correcting deficits in omega-3 supplies will improve cellular membrane function, thus improving intercellular neurotransmitter transport and ultimately restoring normal brain function.

Fish Oil: Protective Against Lung Disease?
Results from studies on the use of fish oil in the treatment of chronic lung diseases—such as emphysema, asthma, bronchitis, and the debilitating genetic disorder, cystic fibrosis—have been both tantalizing and inconclusive. Omega-3 supplementation in diseased subjects has produced encouraging results overall, but there are inconsistencies.

One small study on cystic fibrosis patients found significant improvement, especially decreased inflammation, among those receiving both DHA and EPA for eight months. Patients receiving omega-3s required fewer antibiotics to control chronic lung infections and did better on tests of lung capacity. Other researchers have reported improvements in biochemical markers of disease, but little or no evidence of clinical changes. In the case of asthma, research reveals more improvement among children than adults, but further, larger studies would be required to rule out chance. Trials on smokers have indicated that omega-3s are protective against emphysema and chronic bronchitis, and yield an improvement in spirometry values (a measure of lung capacity). Another trial found a correlation between fish oil consumption and improvement in lung capacity even among non-smokers.43

After reviewing published evidence from around the world, Harvard researcher Joel Schwartz concluded: “…a case can be made for why dietary intakes of PUFAs [polyunsaturated fatty acids (including omega-3s)]…might both be protective against lung disease and ameliorate the normal decline in lung function with age.”40 Schwartz notes, however, that more research is in order: “It is reasonable to study the relation between dietary PUFAs and both lung disease and the normal aging process in the lung.”

Fish oil supplementation, then, holds promise not only as a health-improving strategy for those with lung disease, but also as a hedge against the normal effects of aging on the lungs of otherwise healthy individuals. As Schwartz notes, “There is clear evidence of an effect of omega-3 fatty acids on potential modulators of lung disease.”40 Clearly these intriguing results warrant further investigation and provide another example of the unexpected potential benefits of omega-3s.

Thwarting Cancer with Omega-3s
Studies have shown that omega-3s can slow the growth of experimentally induced cancerous tumors, improve the effectiveness of chemotherapy, and reduce the side effects of chemotherapy and cancer. Several mechanisms of action have been proposed to explain these multiple benefits. Omega-3s may suppress nuclear factor-kappaB activation and bcl-2 expression, allowing cancer cells to self-destruct. Omega-3s may also decrease the rapid growth of both cancer cells and the all-important blood supply that fuels the cells’ unnaturally accelerated growth, by suppressing the expression of cyclooxygenase-2 in tumors. And omega-3s may interfere with the activity of two tumor-promoting genes.

Perhaps most amazing of all, omega-3s may induce cancer cells to differentiate. This is particularly significant, because cancer is a disease characterized by otherwise ordinary cells run amok. Cancer cells are undifferentiated; instead of behaving according to their specific identities (for example, a blood cell behaves as a blood cell, not as a retinal cell), cancer cells “lose their identity,” so to speak. Instead of performing specific duties and following strict “rules” governing growth and dissemination, undifferentiated cancer cells are interested in unbridled growth alone, to the detriment of all else.

“It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients, and improve their quality of life,” concluded one team of researchers.44 Another team noted: “There is both epidemiologic and experimental evidence that the long-chain omega-3 fatty acids…exert protective effects against some common cancers, notably those of breast, colon, and, perhaps, prostate.”37 Other researchers added skin cancer to the list, finding that DHA is more effective at preventing skin cancer than EPA, and noting that a balanced ratio of dietary omega-6 to omega-3 fatty acids may play an important role in this effect.45 As in other areas of omega-3 research, more work needs to be done to further illuminate the potential cancer-preventing properties of omega-3s.