by Craig Weatherby
Technically speaking, the headline on this article is accurate.
But it only means that omega-3 DHA didn’t work as hoped in people who already suffer Alzheimer’s symptoms… and there was no real reason to believe it could.
While it's accurate, our headline is likely misleading, because three prior clinical trials detected DHA-driven benefits in people at earlier stages of dementia... and in those with the leading genetic risk factor for early-onset type Alzheimer’s.
And, we just reported the landmark finding that many Alzheimer’s patients can’t make enough DHA from the omega-3 fat (ALA) found in some plant foods... see “Alzheimer’s Patients Can’t Make Brainy Omega-3”.
So, despite the negative outcome of the new trial, it still seems wise for all people—especially those at higher risk of Alzheimer's—to enjoy seafood frequently and take fish oil as universally advised (500 mg of EPA+DHA daily for healthy persons, or 1,000 mg for heart patients).
Wisely, the authors of the new clinical trial stressed that we need to study omega-3 DHA at earlier stages of dementia, and in healthy people at risk, over longer time periods.
They based their call for more study on the abundance of non-clinical evidence that eating more fish and its omega-3 DHA fat—which is essential to brain survival and functioning—is a no-brainer.
As they wrote in their report, published in the Journal of the American Medical Association (JAMA):
“Several [epidemiological] studies have found that consumption of fish, the primary dietary source of omega-3 fatty acids, is associated with a reduced risk of cognitive decline or dementia. [And] Some studies have found that consumption of DHA, but not other omega-3 fatty acids, is associated with a reduced risk of Alzheimer disease” (Quinn JF et al. 2010).
In addition, as the JAMA editors noted in their press release about the new trial, “Animal studies that used [omega-3] DHA showed reductions in Alzheimer-like brain pathology” (JAMA 2010)... a statement supported by a recent evidence review (Calon F et al. 2007).
Prior trials detected DHA benefits in milder cases and people with a genetic risk
Each of three prior existing clinical trials detected benefits in some people with dementia who took DHA pills… something not mentioned in any of the media coverage we’ve seen so far.
Two Swedish clinical trials detected cognitive benefits from DHA in people at earlier stages of dementia, and in people with a gene variant (APOE 4) linked to increased risk of early onset Alzheimer’s (Freund-Levi Y 2006; 2007). See “Omega-3 DHA Alleviates Agitation in Early-Onset Alzheimer’s”, which links to “Fish Oil May Halt Memory Decline in Alzheimer's”.
Just two years ago, a small but well-designed Taiwanese clinical trial detected DHA-driven brain benefits in patients with mild-to-moderate Alzheimer's or mild cognitive impairment (Chiu CC et al. 2008).
(For more on that trial—and links to some of our reports on studies that support [or don’t] the promise of DHA-rich fish, fish oil, and other marine-source oils for helping delay or deter dementia—see “Omega-3s Boost Aging Brains in Clinical Trial”.)
The positive outcomes of the Swedish and Taiwanese trials support a key point made by the authors of the new trial:
“Because part of the rationale for the trial was epidemiological evidence that DHA use before disease onset modifies the risk of Alzheimer disease, it remains possible that an intervention with DHA might be more effective if initiated earlier in the course of the disease in patients who do not have overt dementia” (Quinn JF et al. 2010).
And they went on to make a very key point: “Individuals [who are in a mental state that’s] intermediate between healthy aging and dementia, such as those with mild cognitive impairment, might derive benefit from DHA supplementation….”
Of course, while that hypothesis is supported by ample cell and animal evidence, it needs to be confirmed by long-term clinical trials in younger people… including those with and without known risk factors for dementia.
What the new trial did… and found
The new clinical study was led by Joseph F. Quinn, M.D., of Oregon Health and Science University and involved scientists from Yale, the Mayo Clinic, UCLA, UCSF, and others.
Dr. Quinn’s team conducted a randomized, placebo-controlled trial designed to discover whether DHA supplements would slow the rate of cognitive and functional decline in people with mild-to-moderate Alzheimer's disease.
The 18-month-long study started with 402 people, and 295 finished the trial.
Each participant was randomly assigned to take either omega-3 DHA (2 grams per day) or an identical placebo pill … among the 295 people who completed the trial, 58 percent (171) were in the DHA group and 42 percent (124) were taking placebo pills.
Changes in cognitive and functional abilities were assessed using two standard tests (ADAS-cog and CDR), administered several times during the 18-month duration of the trial.
The researchers found that daily DHA supplements did not improve test scores significantly in any subgroup of participants: “In summary, these results indicate that DHA supplementation is not useful for the population of individuals with mild to moderate Alzheimer disease” (Quinn JF et al. 2010).
The researchers also used MRI scans to measure any increases or decreases in brain atrophy in 102 participants.
MRI scans taken at the beginning and end of the trial did not show any increase in brain volume among those taking DHA—which could indicate growth of new brain cells (neurons)—versus the placebo group.
We heartily endorse the authors’ call for more clinical trials… ones that involve people at younger ages, at earlier disease stages, and in healthy people at known risk of decline.
Calon F, Cole G. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):287-93. Epub 2007 Nov 26. Review.
Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY. The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44. Epub 2008 May
Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M. Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry. 2007 Jun 21; [Epub ahead of print]
Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.
JAMA and Archives Journals (JAMA). DHA 'fish oil' supplements do not seem to slow cognitive, functional decline in Alzheimer's disease. November 2, 2010. Accessed at http://www.eurekalert.org/pub_releases/2010-11/jaaj-do102810.php
Quinn JF et al. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA. 2010;304(17):1903-1911. doi:10.1001/jama.2010.1510