Saturday, July 21, 2007

Health benefits of omega-3 fatty acids

Omega-3 fatty acids are now getting credit for health benefits in a surprising range of disease conditions.

Just to review a little, fats and fatty acids are said to be saturated if they have the maximum possible number of hydrogen atoms attached. In particular, a fatty acid is unsaturated if it has at least one double C-C bond on its main hydrocarbon chain. (An atom of hydrogen could potentially be attached there.) It is polyunsaturated if it has at least two. By definition, an omega-3 fatty acid is polyunsaturated, and in addition one of its double bonds occurs as close as possible to the end of the main chain that is opposite the carboxyl (COOH) group required in a fatty acid.

Curiously enough, this simple chemical property – rather than any more complicated chemical configuration – appears to be sufficient to confer a variety of health benefits on omega-3 fatty acids.

Perhaps the best-known benefit, for which there is evidence in studies of particular (not all) omega-3 fatty acids, is related to coronary heart disease (e. g. atherosclerosis or "hardening of the arteries"). The omega-3 fatty acids most frequently involved are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

But recent research has encompassed many other disease conditions, for example, abnormal blood vessel growth that can cause blindness, such as that which may occur in retinopathy of premature infants, diabetic retinopathy, and "wet" age-related macular degeneration.

Omega-3 fatty acids protect eyes against retinopathy, study finds
The researchers studied the effect of the omega-3 fatty acids EPA and DHA, derived from fish, and the omega-6 fatty acid arachidonic acid on the loss of blood vessels, the re-growth of healthy vessels, and the growth of destructive abnormal vessels in a mouse model of oxygen-induced retinopathy. The retinopathy in the mouse shares many characteristics with retinopathy of prematurity (ROP) in humans. ROP is a disease of the eyes of prematurely born infants in which the retinal blood vessels increase in number and branch excessively, sometimes leading to bleeding or scarring. Infants who progress to a severe form of ROP are in danger of becoming permanently blind. There are also aspects of the disease process that may apply to diabetic retinopathy, a disease in which blood vessels swell and leak fluid or grow abnormally on the surface of the retina, and age-related macular degeneration (AMD), a disease of the macula, the part of the retina responsible for central vision, and a leading cause of vision loss in Americans 60 years of age and older.

Typical Western diets are lacking in omega-3 fatty acids, which are found mainly in shellfish and oily fish (e. g. salmon, sardines), and instead have a much higher percentage of omega-6 fatty acids. (In an omega-6 fatty acid, the only difference is that the first C-C double bond occurs farther from the end of the hydrocarbon chain that is opposite the carboxyl group. See these Wikipedia articles for more details: essential fatty acids, essential fatty acid interactions.) It turns out, oddly enough, that omega-6 fatty acids can have deleterious effects, just the opposite of omega-3 effects.
The researchers found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet reduced the area of vessel loss that ultimately causes the growth of the abnormal vessels and blindness. Omega-6 fatty acid contributes to the growth of abnormal blood vessels in the retina.

To further test the apparent beneficial effect of omega-3 fatty acids, the researchers studied mice fed a diet modeled after a traditional Japanese diet (more omega-3 than omega-6 fatty acids) and mice fed a diet modeled after a traditional Western diet (lower amounts of omega-3 fatty acids). In addition, they studied mice genetically altered with a gene which mammals normally lack that converts omega-6 into omega-3 fatty acids. They found that the mice with higher amounts of omega-3 had a nearly 50 percent decrease in retinopathy.

Most importantly, this research identified a likely mechanism of action by which omega-3 fatty acids confer their benefits. The mechanism involves suppression of inflammation, especially involving the inflammatory cytokine TNF-α. In particular, this would apply to atherosclerosis, in which inflammation is generally regarded as a significant problem. Such anti-inflammatory properties, if indeed present, could account for the benefits of omega-3 fatty acids in other circumstances also. Another report on the same research describes this:

Can Blindness Be Prevented Through Diet?
Omega-3 fatty acids like DHA and EPA are thought to dampen inflammation in the body. ...

The researchers demonstrated that the omega-3-based diet suppressed production of TNF-alpha, reducing the inflammatory response in the retina, whereas the omega-6-based diet increased TNF-alpha production. The retinas of omega-3-fed mice also had increased production of the anti-inflammatory compounds neuroprotectinD1, resolvinD1 and resolvinE1. These compounds, derived from omega-3 fatty acids, also potently protected against pathological vessel growth, and they were not detected in the retinas of mice fed the omega-6 diet.


Cancer is a rather more controversial case in connection with possible health benefits of omega-3 fatty acids. Many epidemiological studies have been done to try to identify cancer-protective effects of omega-3 in the diet, with varying results. Meta-analysis of such studies does not identify a conclusive connection. However, such studies are hampered by uncertainties about the actual diets consumed by participants. Additionally, a lot may depend on individual genetic factors. In animal studies it is possible to be much more quantitatively precise. For instance, we have this:

Omega-3 Fatty Acids May Help Slow Prostate Cancer Growth
The mice were fed either a diet high in omega-3 (ratio of omega-6 to omega-3 was 1:1) a diet low in omega 3 (ratio omega-6 to omega-3 was 20:1), or a diet high in omega-6 (ratio of omega-6 to omega-3 was 40:1). The scientists compared survival rates and weighed the animals' prostates to measure tumor progression.

Mice with the tumor suppressor gene remained free of tumors and had 100 percent survival, regardless of diet. In mice with the gene defect, survival was 60 percent in animals on the high omega-3 diet, 10 percent in those on the low omega-3 diet and 0 percent in those on the high omega-6 diet.

"This suggests that if you have good genes, it may not matter too much what you eat," said [senior researcher Yong Q.] Chen, a professor of cancer biology. "But if you have a gene that makes you susceptible to prostate cancer, your diet can tip the balance. Our data demonstrate the importance of gene-diet interactions, and that genetic cancer risk can be modified favorable by omega-3 PUFA."


In a rather different direction, there has been a lot of suspicion, and some epidemiologial and experimental evidence, that omega-3 fatty acids and higher omega-3:omega-6 ratios have beneficial effects in connection with psychological and mood disorders. So it makes sense that omega-3 could be useful with the symptoms of agitation and depression associated with Alzheimer's disease. It turns out that benefits may be significantly dependent on genetic factors related to the disease:

Omega-3 Supplements Can Help With Alzheimer's Symptoms, Study Suggests
Omega-3 supplements can, in certain cases, help combat the depression and agitation symptoms associated with Alzheimer's disease, according to a clinical study conducted at the Swedish medical university Karolinska Institutet.

A number of epidemiological studies have shown that eating fatty fish provides a certain degree of protection against Alzheimer's and other dementia diseases--an effect often thought attributable to the omega-3 fatty acids it contains. Some studies also suggest that omega-3 can have a therapeutic effect on some psychiatric conditions.

The results were not straightforward, to put it mildly. There is a well-known susceptibility gene for Alzheimer's, APOE4. Carriers of the gene experienced benefits for agitation symptoms, while non-carriers had benefits for depression symptoms!
There was no observable difference in therapeutic effect between the patients receiving the omega-3 and the placebo group. However, when the researchers took into account which of the patients carried the susceptibility gene APOE4 and which did not, an appreciable difference appeared. Carriers of the gene who had received active treatment responded positively to the omega-3 as regards agitation symptoms, while non-bearers of the gene showed an improvement in depressive symptoms.


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