Trade.Information

Topic Name: UCLA scientists have shown that fish oil is good for Alzheimer's disease

Category: Biomedical

Research persons: Greg Cole, PhD

Location: University of California , Los Angeles, United States

Details

It's good news that we are living longer, but bad news that the longer we live, the better our odds of developing late-onset Alzheimer's disease.

Many Alzheimer's researchers have long touted fish oil, by pill or diet, as an accessible and inexpensive "weapon" that may delay or prevent this debilitating disease. Now, UCLA scientists have confirmed that fish oil is indeed a deterrent against Alzheimer's, and they have identified the reasons why.

Reporting in the current issue of the Journal of Neuroscience, now online, Greg Cole, PhD, professor of medicine and neurology at the David Geffen School of Medicine at UCLA and associate director of UCLA's Alzheimer Disease Research Center, and his colleagues report that the omega-3 fatty acid, docosahexaenoic acid (DHA) found in fish oil increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the "plaques" associated with the disease.

The plaques are deposits of a protein called beta amyloid that is thought to be toxic to neurons in the brain, leading to Alzheimer's. Since having high levels of LR11 prevents the toxic plaques from being made, low levels in patients are believed to be a factor in causing the disease.

Alzheimer's is a debilitating neurodegenerative disease that causes memory loss, dementia, personality change and ultimately death. The national Alzheimer's Association estimates that 5.1 million Americans are currently afflicted with the disease and predicts that the number may increase to between 11 million and 16 million people by the year 2050.

The researchers examined the effects of fish oil, or its component DHA, in multiple biological systems and administered the oil or fatty acid by diet and by adding it directly to neurons grown in the laboratory.

"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," said Cole, who is also associate director of the Geriatric Research Center at the Veterans Affairs Medical Center.

To show that the benefits of DHA were not limited to nonhuman animal cells, the researchers also confirmed a direct impact of DHA on human neuronal cells in culture as well. Thus, high levels of DHA leading to abundant LR11 seem to protect against Alzheimer's, Cole said, while low LR11 levels lead to formation of the amyloid plaques.

Fish oil and its key ingredient, omega-3 fatty acids (found in fatty fish like salmon), have been a mainstay of alternative health practitioners for years and have been endorsed by the American Heart Association to reduce the risk of cardiovascular disease.

Fatty acids like DHA are considered "essential" fatty acids because the body cannot make them from other sources and must obtain them through diet. Years of research have shown that DHA is the most abundant essential fatty acid in the brain, Cole said, and that it is critical to fetal and infant brain development. Studies have also linked low levels of DHA in the brain to cognitive impairment and have shown that lower levels may increase oxidative stress in the brains of Alzheimer's patients.

Based on the positive results, the National Institutes of Health is currently conducting a large-scale clinical trial with DHA in patients with established Alzheimer's disease. For those patients, Cole said, it may be too late in the disease's progression for DHA to have much effect. But he is hopeful that the NIH will conduct a large-scale prevention clinical trial using fish oil at the earliest stages of the disease — particularly because it is unlikely that a pharmaceutical company will do so, since fish oil in pill form is readily available and inexpensive.

Still to be determined, he said, "is what the optimal dose should be. It could be that a smaller amount might be helpful, especially in a place like the south of France, where people are already on a Mediterranean diet."

Here in the United States, though, where fish consumption is not very high, the dose may need to be higher.

"There's a deficiency of DHA to begin with," Cole said, "and this may contribute to the low LR11 seen in many Alzheimer's patients."

Note for Alzheimer's disease

Alzheimer's disease (AD), also called Alzheimer disease, and simply known as Alzheimer's, is a neurodegenerative disease that, in its most common form, is found in people over the age of 65. Approximately 24 million people worldwide have dementia of which the majority (~60%) is due to Alzheimer's.
Clinical signs of Alzheimer's disease are characterized by progressive cognitive deterioration, together with declining activities of daily living and by neuropsychiatric symptoms or behavioral changes. It is the most common type of dementia. Plaques which contain misfolded peptides called amyloid beta (Aβ) are formed in the brain many years before the clinical signs of Alzheimer's are observed. Together, these plaques and neurofibrillary tangles form the pathological hallmarks of the disease. These features can only be discovered at autopsy and help to confirm the clinical diagnosis. Medications can help reduce the symptoms of the disease, but they cannot change the course of the underlying pathology.

Note for Omega-3 fatty acid

ω−3 fatty acids (commonly spelled omega-3 fatty acids) are a family of polyunsaturated fatty acids which have in common a carbon-carbon double bond in the ω−3 position.
Important nutritionally essential ω−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). For a more complete list, see list of ω−3 fatty acids. The human body cannot synthesize ω−3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated ω−3 fatty acids from the eighteen-carbon ω−3 fatty acid, α-linolenic acid. These conversions occur competitively with ω−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the ω−3 α-linolenic acid and ω−6 linoleic acid are essential nutrients which must be obtained from food. Synthesis of the longer ω−3 fatty acids from linolenic acid within the body is competitively slowed by the ω−6 analogues. Thus accumulation of long-chain ω−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of ω−6 analogs do not greatly exceed the amounts of ω−3.

Note for Docosahexaenoic acid

Docosahexaenoic acid is an omega-3 essential fatty acid. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end.
DHA is most often found in fish oil. Most of the DHA in fish and other more complex organisms originates in microalgae of the genus Schizochytrium, and concentrates in organisms as it moves up the food chain. DHA is also commercially manufactured from Crypthecodinium cohnii. Most animals make very little DHA through metabolism; however small amounts are manufactured internally through the consumption of α-linolenic acid, an omega-3 fatty acid found in chia, flax, and many other seeds and nuts.
DHA is metabolized to form the docosanoids—several families of potent hormones. DHA is a major fatty acid in sperm and brain phospholipids, and especially in the retina. Dietary DHA can reduce the level of blood triglycerides in humans, which may reduce the risk of heart disease. Low levels of DHA result in reduction of brain serotonin levels and have been associated with ADHD, Alzheimer's disease, and depression, among other diseases, and there is mounting evidence that DHA supplementation may be effective in combating such diseases (see external links at the end of this article).

Note for Amyloid beta

Amyloid beta (Aβ or Abeta) is a peptide of 39-43 amino acids that is the main constituent of amyloid plaques in the brains of Alzheimer's disease patients. Similar plaques appear in some variants of Lewy body dementia and in inclusion body myositis, a muscle disease. Aβ also forms aggregates coating cerebral blood vessels in cerebral amyloid angiopathy. These plaques are composed of a tangle of regularly ordered fibrillar aggregates called amyloid fibers, a protein fold shared by other peptides such as prions associated with protein misfolding diseases.
Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function. APP can be processed by α-, β- and γ-secretases; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 39-43 amino acid residues in length. The most common isoforms are Aβ40 and Aβ42; the shorter form is typically produced by cleavage that occurs in the endoplasmic reticulum, while the longer form is produced by cleavage in the trans-Golgi network.

In addition to Cole, authors included Qui-Lan Ma, Bruce Teter, Oliver J. Ubede, Takashi Morihara, Dilsher Dhoot, Michael D. Nyby, Michael L. Tuck and Sally A. Frautschy, all of UCLA.

Funding for the research was provided by a grant from the National Center for Complementary and Alternative Medicine. The research was initiated with support from the National Institute on Aging.