Fish Oil and Molecular Pathways in Alzheimers

It has been suspected for some time that taking fish oil may reduce the risk of developing age-related Alzheimers disease. Fatty fish, like salmon, are rich in oils which contain omega-3 acids. Omega-3's cannot be manufactued by the body and must be acquired through diet or vitamins.

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New research from UCLA's Dr. Greg Cole has now shown that these acids (also called docosahexaenoic acid or DHA) increases the production of a protein called LR11, which in turn has been confirmed to destroy the protein that forms beta-amyloid plaques. LR11 can reduce beta-amyloid production by guiding APP (the precursor of amyloid) in recycling Golgi and early endosome pathways, thus trafficking it away from beta- and alpha-secretase. Without interaction with the secretases, the harmful amyloid protein cannot form and aggregate into neuronal plaques. These plaques, along with neurofibrillary tau tangles, are the pathological features of Alzheimers, and are responsible for the slow degeneration of Alzheimer's patients' brains.

"We found that even low doses of DHA increased the levels of LR11 in rat neurons, while dietary DHA increased LR11 in brains of rats or older mice that had been genetically altered to develop Alzheimer's disease," Cole said in a statement.

Published in this month's Journal of Neuroscience, abstract here.

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Just a question from a non-biologist: "taking fish oil may reduce the risk..." could imply that it reduces the risk for those who have a "normal" diet anyway?

Yes the evidence is certainly accumulating that those acids are essential for those functions, in the same way that vitamins are undeniably essential for other functions, I did not see (or understand) the evidence that taking additional fish oil, in the form of supplements, would be beneficial on top of a normal balanced diet?

I always thought that fish oil sounded like one of those supplements of dubious merit that litter the aisles of health food stores everywhere. Then I went to a talk in which the researcher had done some really great computational modeling of model lipid bilayers with different amounts of omega-3 FAs, and I started thinking there might be something to it.

Now, I think it might be time to go pick up a bottle of pills :)

RNB: As for whether taking fish oil, in addition to a 'healthy diet,' could lower Alzheimer's risk...

The rats used in the study were models of human Alzheimer's disease, and they all had a 100% chance of developing the disease. The fate of the average human is not so certain-- you may or may not have a genetic predisposition to developing Alzheimer's disease and waiting until you are diagnosed to begin taking fish oil is probably useless. Perhaps it is better to assume the worst and take the fish oil, in the event that you are one of the unlucky ones who has the polymorphism.

Many Americans who develop age-related Alzheimers (AD) have perfectly normal, if not optimized diets. Living long enough to develop AD might be taken to mean that your body is quite healthy. And as the diet in America has been getting better (higher calories, etc) over the years, the incidence of AD has also increased in America. Conversely, many nations which consume lots of fish in their diet, like Japan, have not only long life but reduced incidence of AD. This is circumstantial evidence until it was found that the omega 3 acids actually influence the formation of amyloid beta plaques, suggesting that the threshold of beneficial AD-reducing effects of omega-3 acids is not being obtained in the current American diet. This is an empirical question, but as for me, like Jason, it certainly isn't going to hurt to take the fish oil.

I was under the impression that DHA was also essential to the myelin which sheaths neurons, and thus is a good supplement to prenatal vitamins.

Does the study say if the rats showed lessened Alzheimers or just that they found higher amounts of LR11?

That seems to be kind of an important difference. (The abstract is gobbledygook to me; I can't tell.)

I've read only the abstract, which made my eyes glaze over, but I know that there are at least three kinds of omega-3. Although DHA was the kind tested in this study, might the results apply to ALA or EPA as well?

My original comment hinted at my unease at the tone of the headline, and indeed the first sentence, but I think that Jennifer has articulated it better. In England there was a very dubious trial of fish oil supplements, the link is to Ben Goldacre's analysis of it.

Again, no issue with the science. Just unease with the jump from genuine discovery that certain chemicals are required for certain functions straight to "eat more of x".

I always thought that fish oil sounded like one of those supplements of dubious merit that litter the aisles of health food stores everywhere.

There have been a number of dubious claims for omega-3 fats over the last decade, to be sure. However, their role in aiding cardiovascular health appears to be quite well-founded; even the fairly conservative American Heart Association has issued recommendations to eat more omega-3 fatty acids, particularly the long chain EPA and DHA, and it cautiously recommends supplements for people who have documented heart disease.

Research into the effects of omega-3 fats on other aspects of health (e.g., brain function) has been a lot more scattered and lower quality. Much of it has been initially spectacular but then not backed up by confirming research. Given the research on cardiovascular health, though, eating more omega-3 fat in general is probably a really good idea.

By ColoRambler (not verified) on 27 Dec 2007 #permalink

King Rat - you're right, they looked at levels of LR11 but did not present data on whether the mice developed Alzheimer's type pathology. I'm not familiar with the model or the techniques really, but couldn't they have been taking a microtome slice of each mouse brain to look for plaques and tangles before they tossed them in the blender? Does this mouse model of alzheimers develop those structures?

Title changed, although I don't agree with Jennifer's assessment. I'll post on why later.

Hey Shelley! Can you get ScienceDaily to change their title, too? I can't help but wonder if some of these studies aren't funded by the fishing industry. Obviously, you're not incorrect to say that fish oil does x or y, it's just that those fatty acids are found in other sources. And perhaps, in the case, of DHA, fish is ultimately is the best source. I just oppose fueling demand for fish (fish oil would be preferable) without addressing some of the deeper-seated issues with our diet and omega-3s and especially without also cautioning against the health risks of consuming more fish (e.g., mercury).

Hi Jennifer, ok well thats all I was really going to say then: that it was fish oil that had an effect so the title was not inaccurate. Although I certainly see your point about promoting unmitigated fish consumption--and how that might lead to increased mercury--but many fish like sardines and herring are low in mercury and high in DHA. And as your commenters pointed out, fish oil is by far the most abundant source of DHA, and other routes of intake are pricy and inefficient. Fish oil supplements get around the mercury problem altogether, as it is purified and standardized. And as pointed out by commenters here, fish oil has benefits outside of this study, specifically it can regulate cholestorol and has anti-inflammatory and neuroprotective properties.

Shouldn't the focus be on how to make fishing sustainable rather than telling people *not* to eat fish, given the benefits?


As to whether the study shows that fish oil may *actually* decrease Alzheimers risk:

This study shows that dietary fish oil increases the protein LR11, which provides the specific molecular mechanism that fish oil affects amyloid production. It had already been determined in 2005 that administering dietary DHA reduced neurotoxic amyloid plaque load ( The current paper shows us *why* that is the case by implicating the DHA-dependent protein LR11 in the molecular processing of amyloid.

Hi Shelley. (Cross-posted at Shifting Baselines) This from Joel Fuhrman, M.D..

Docosahexaenoic acid (DHA) is a long-chain omega-3 fatty acid. About half of the brain and eyes are made up of fat, much of which is DHA, which is an essential nutrient for optimal brain and eye function.1 Children's diets today are notoriously low in the beneficial omega-3 fats found in foods such as walnuts, flax seeds, soybeans, leafy greens, and certain fish. I do not recommend fish as a preferred source of these beneficial fats for children because of contamination with pollutants and mercury.

The most commonly used supplement to add DHA to the diet is fish oils, but what is not widely known is that most of us can produce sufficient DHA from short-chain omega-3 fatty acids received from walnuts, flax seeds, and green vegetables. Many fish make their DHA from eating greens, too, from algae.

New products are available that contain DHA from algae, the fish's original source. Unlike fish oil, the algae-derived DHA, grown in the laboratory, is free of chemical pollutants and toxins that may be present in some fish oil-based brands. I recommend favorable DHA products that are designed for purity and are suitable for children. Neuromins is a common (non-fish-derived) brand of DHA sold in most health food stores, and I also have designed and manufactured an all-plant-derived DHA supplement, DHA Purity, available on my Web site and in my office.

In this case, I am not telling people not to eat fish (though I will be happy to). I am merely saying that we should be looking at alternative sources of DHA given that, at the moment, very few fish stocks are indeed sustainable and there are associated health risks (in addition to benefits) when consuming fish. It is even more important that we ask ourselves why we're so deficient in DHA to begin with when many of our ancestors actually ate LESS fish than we eat today. And then I come back to Michael Pollan and our corn-based society...

p.s. Great parrot banner.

FYI the study was not funded by the fishing industry, but rather the National Center for Complementary and Alternative Medicine and the National Institute of Aging.

I quite agree that alternative sources for DHA should be pursued, however it was correct that fish oil was the DHA source used in this study, and that it did increase proteins known to protect from Alzheimers. The algae source looks promising. I just checked the paper again and saw that the rats with the best results were fed a 2.2% fish oil diet, with intermediate results at 1.1%. For a human, that would be a significant amount of DHA supplement per month.

Just an FYI: Unfortunately for some (myself), Fish Oil supplements seem intolerable to the digestive system. I have never had significant adverse digestive reactions to any medications or supplements until I recently started taking fish oil geltabs. I even tried taking one tab daily instead of the suggested two, but it wreaks havoc in my poor belly.

By GeorgesArt (not verified) on 29 Dec 2007 #permalink

I'll need to dig up the article, but wasn't there some issue with Fish Oil as a supplement vs eating fish? To clarify, the supplements for Omega-3 won't necessarily give you what your looking for, you need to consume the actual food, like fish, for it to provide any benefit.

I believe the idea behind the article was something along: eat the food, not the nutrients.

Kirk T's point aside (I haven't seen anything to that effect)

For those who are looking, there is a vegan/vegetarian source of both DHA and EPA. It's called V-Pure and here's the link:

It's a little pricey but I think totally worth it for a sustainable product.