Findings help explain why studies link higher omega-3 intake to reduced dementia rates
by Craig Weatherby
We’ve reported on several studies that link higher fish or omega-3 intake with reduced risk of Alzheimer’s disease and more common forms of dementia.
While statistical correlations like these cannot prove a cause-effect relation, they encourage funding of further research.
The National Institutes of Health is now conducting a large-scale clinical trial to test the effects of supplemental DHA in patients with established Alzheimer's disease.
However, the results of preliminary clinical trials suggest that omega-3s are unlikely to have a substantial effect once the disease progresses beyond the earlier diagnosable stages.
However, new kinds of brains scans are making it possible to detect the presence of brain "plaques" well before any symptoms appear.
This development raises the value of any safe drug or food factor that works best at early stages in the development of dementia.
For instance, the results of a six-month trial in which mild to moderate Alzheimer's patients received fish oil found no impact on cognitive decline in the overall group, but some benefit in patients at the earliest stages of cognitive decline.
As the authors wrote, “… our study indicated that the omega-3 fatty acid preparation conferred a slower decline of cognition in those with the mildest impairment compared with placebo control subjects with a similar degree of cognitive dysfunction at the start of the study.” (See “Fish Oil May Halt Memory Decline in Alzheimer's”.)
Leading researchers have urged the NIH to urgently conduct a large-scale prevention clinical trial using fish oil at the earliest stages of the disease.
(No pharmaceutical company will fund such research, since omega-3s are abundant in fish and fish oil, and drug companies will only test patentable compounds that promise huge profits in return for their hundreds of millions in development and marketing outlays.)
Now exciting new research results shed more light on the ways in which omega-3s may help deter the dread mental disease.
Researchers from UCLA's Alzheimer Disease Research Center report finding that DHA—the "brainiest" of the two key omega-3s in fish—increases levels of a brain-plaque-busting protein that’s scarce in older Alzheimer's patients (Ma QL et al 2007).UCLA study pinpoints another protective potential in omega-3s
This natural brain compound—called LR11—reduces production of beta-amyloid protein, which forms the cell-destroying “plaques” associated with Alzheimer's disease.
Genetic traits that reduce LR11 levels in the brain are associated with increased risk of Alzheimer's disease.
However, these undesirable genetic traits only appear in small percentage of Alzheimer's patients with low brain levels of LR11.
This suggests that environmental or dietary factors may be responsible for loss of LR11 in most Alzheimer's patients. And this likelihood increases the significance of the new study’s finding that DHA raises LR11 levels in rodents’ brains and in isolated human brain cells.
As Dr. Cole said in a UCLA press release, “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.”
His team also confirmed that DHA raised LR11 levels in isolated human brain cells. Thus, according to Cole, “high levels of DHA leading to abundant LR11 seem to protect against Alzheimer’s, while low LR11 levels lead to formation of the amyloid plaques” (UCLA 2007).
DHA counters brain-damaging effects of fructose and diabetesEpidemiological studies indicate that the insulin resistance associated with normal aging and diabetes is a significant risk factor for developing Alzheimer's disease.
So, the UCLA group tested DHA’s ability to increased LR11 protein levels in rodents made insulin-resistant by a diet rich in high-fructose corn syrup.
(Dietary fish oil has been shown to reduce oxidative stress—a risk factor for Alzheimer’s—in pre-diabetic animals like these.)
After using the corn syrupy diet to induce insulin-resistance in the rodents, they fed them a fish-oil-fortified diet for eight weeks. This change increased the animals’ brain levels of LR11 protein significantly, compared with rats on a fructose-rich diet without fish oil.
The results of all phases of the study highlight the dangers of America’s chronically omega-3-deficient diet.
As Dr. Cole lamented, “There's a deficiency of DHA [among Americans] to begin with, and this may contribute to the low LR11 seen in many Alzheimer's patients” (UCLA 2007).
The UCLA team’s conclusion is worth quoting: “Our data and the clinical trial results suggest that DHA may be most useful for early intervention and prevention of late-onset Alzheimer's disease” (Ma QL et al 2007).
- Ma QL, Teter B, Ubeda OJ, Morihara T, Dhoot D. Nyby MD, Tuck ML, Frautschy SA, Cole GM. Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention. The Journal of Neuroscience, December 26, 2007 • 27(52):14299 –14307.
- Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40.
- Cole GM, Lim GP, Yang F, Teter B, Begum A, Ma Q, Harris-White ME, Frautschy SA. Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions. Neurobiol Aging. 2005 Dec;26 Suppl 1:133-6. Epub 2005 Nov 2. Review.
- Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health. 2006;18(3):249-59. Review.
- UCLA Health Sciences. Why Fish Oil Is Good for You. Accessed online December 25, 2007 at http://www.newswise.com/articles/view/536485/.