Results of two clinical trials should prompt research into the anti-dementia potential of antioxidants and fatty fish
by Craig Weatherby
The encouraging results of two small clinical trials were released this past week.
Both trials—one from the Pacific Northwest and one in Taiwan—tested the effects of omega-3-rich fish oil on people suffering from moderate Alzheimer's disease and/or milder cognitive impairments.
The Taiwanese paper made some headlines, but the U.S. findings, from a longer-lasting clinical trial, seem even more significant.
But the U.S. team's paper—presented last April at the American Academy of Neurology's annual meeting—seems to have been overlooked by the media.
Taken together, the positive findings from the U.S. and Taiwan should prompt scientists to conduct larger trials.
Let's take a look at both studies, starting with the trial performed in part by researchers from our home state of Washington.
Northwest team finds omega-3s and key antioxidant aid Alzheimer's patients
Their goal was to test the effects of two promising nutrients in Alzheimer's patients: omega-3s and lipoic acid.
They divided 39 participants into three groups, each of which took their assigned capsule daily for one year:
- Omega-3 fish oil (3 grams per day)
- Omega-3 fish oil (3 grams per day) + lipoic acid (600 mg per day)
As readers of the bestsellers by nutrition-savvy dermatologist Dr. Nick Perricone know, lipoic acid is a critical bodily antioxidant of unique versatility and potency.
The Northwest team tested the volunteers for mental performance, using the standard Mini Mental State Exam (MMSE) and Activity of Daily Living (ADL) tests.
Thirty-two people completed the 1-year trial, and the results were both exciting and encouraging:
- The omega-3 + lipoic acid group had the best MMSE scores.
- Both the omega-3-only and omega-3 + lipoic acid groups showed significantly better scores on the Activity of Daily Living (ADL) test.
As the researchers wrote, "the significant positive results… warrant further investigation...” (Shinto L et al. 2008).
This seems like the understatement of the year.
Northwest trial’s results affirm same team's earlier findings
The Northwest team was following up on a study they’d published earlier this year.
In that investigation, the blood of healthy people and people diagnosed with Alzheimer’s disease (AD) was tested for carotene antioxidants (e.g., beta-carotene, lutein) and long-chain omega-3s from fish or fish oil (EPA and DHA).
Dietary carotenes come primarily from colorful fruits and vegetables (and salmon), while long-chain omega-3s come primarily from fish or fish oil
They found that the Alzheimer’s patients with the worst scores on mental tests also had the lowest levels of carotenes and omega-3s.
As they wrote, “The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD” (Wang W et al. 2008).
These results were preceded by positive findings from a similar Irish study, which correlated low levels of omega-3s with higher risk of Alzheimer’s: “… [blood omega-3 EPA] and [omega-3] DHA levels were significantly lower in all … patients with Alzheimer's disease compared with control values” (Tully AM et al. 2003).
And the Irish team’s results were preceded by positive findings from a Canadian research group: “… low levels of omega-3 fatty acids in the plasma [blood] may be a risk factor for cognitive impairment and/or dementia. Interestingly, a decreased level of [omega-3] DHA was not limited to the AD patients but appears to be common in cognitive impairment with aging” (Conquer JA et al. 2000).
Dementia dread: Personal fear and public concern
The generic term “dementia” refers to any progressive brain dysfunction that leads to a gradually increasing restriction of daily activities. The best-known and most common type of dementia is Alzheimer’s disease.
Dementia is defined as an acquired persistent impairment in intellectual function with compromise in at least three of the following: 1) language, 2) memory, 3) visual-spatial skills, 4) emotion/personality, 5) cognition (abstraction, calculation, and judgment).
Symptoms of dementia include memory loss, cognitive disorientation and behavioral changes. Dementia affects not only patients but also those surrounding them, as most patients require long-term care.
This makes dementia an especially devastating disease, and one that rapidly aging societies worldwide urgently need to find ways to deter.
Taiwanese study lends support
Earlier this month, the clinical findings from Seattle received support from a randomized, double-blind, placebo-controlled clinical trial of shorter length and comparable size (Chiu CC et al. 2008).
This trial lasted only one-third as long as the one-year U.S. trial, and involved older people, whose dementia may have been more advanced.
Doctors at Taiwan’s Taipei City Hospital recruited 46 people, 23 of whom had been diagnosed with mild or moderate Alzheimer’s disease and 23 of whom had been diagnosed with mild cognitive decline. Their average age was 75.3 years.
People from each group were randomly assigned to receive one of two daily supplements:
- Fish oil capsules providing 1.8 grams of omega-3s (EPA + DHA).
- Placebo (olive oil) capsules.
The doctors tested the participants’ disease state and mental acuity at the beginning and end of the study, using two standard measures:
- The Clinician’s Interview-Based Impression of Change Scale (CIBIC-plus) assesses disease severity and progression.
- The Alzheimer’s Disease Assessment Scale (ADAS-cog) assesses specific cognitive abilities.
Among the 35 participants who finished the study, those who received the omega-3 supplements scored higher (better) on the CIBIC-plus tests of disease severity and progression.
There were no significant differences between the scores that the fish oil and placebo groups received on the ADAS-cog test.
However, when the researchers looked more closely, they detected a “significant improvement in ADAS-cog” among the people diagnosed with mild cognitive decline (Chiu CC et al. 2008).
In contrast, they detected no improvement in the participants diagnosed with mild or moderate Alzheimer’s disease, whose cognitive condition was considerably worse to begin with.
Accordingly, the Taiwanese concluded that the cognitive benefits of omega-3 fatty acids might be stronger in patients with mild cognitive impairment, compared with people diagnosed with Alzheimer’s disease.
Lending support to the presumption that the omega-3s were responsible, the people with higher proportions of omega-3 EPA in their red blood cell membranes were also those who scored better on the cognition tests.
To read more summaries of research into the associations between diet and brain health, search our newsletter archive for “brain” or “Alzheimer’s”.
Dementia risk tied to weight, cholesterol, education and gender
Earlier this month, researchers at the University of California at Irvine (UCI), led by Dr. Claudia Kawas, published some findings from their ongoing “90+ Study”.
The researchers reviewed an analysis of 911 people enrolled in the 90+ Study.
Of those, 45 percent of the women had dementia, as opposed to 28 percent of the men. The analysis did not determine when the subjects first experienced dementia (Corrada MM et al. 2008).
The UCI team found that the likelihood of having dementia doubled every five years in women after reaching 90, but not in men.
The results also showed that women with a higher education were as much as 45 percent less likely to have dementia compared to women with less education.
Men show early symptoms before women
A paper presented last April at the American Academy of Neurology meeting in Chicago suggests that men have their own problems.
Researchers from the Mayo Clinic studied 2,050 people between the ages of 70 and 89, living in Olmsted County, Minnesota.
Among this group, men were one-and-a-half times more likely than women to suffer mild cognitive impairment, which is the transition stage before dementia.
But as the authors wrote, other studies have found that more women than men (or an equal proportion) have dementia, so their findings suggest the possibility of a delayed progression to dementia in men, or a faster progression among women (Roberts RO et al. 2008).
Dementia tied to obesity and cholesterol: Omega-6 overload is the hidden villain
Two other papers presented at the American Academy of Neurology meeting suggest links between increased risk of dementia and obesity and total cholesterol levels.
It appears that obesity may increase the risk of dementia by up to 80 percent (Beydoun MA et al. 2008).
And the risk of the Alzheimer’s may rise in tandem with total cholesterol levels. Researchers reported finding that the people with the highest levels (greater than 249-500 mg/dl) at age 40 to 45 were 50 percent more likely to have developed Alzheimer’s 30 years later. (Solomon A et al. 2008)
High total-cholesterol levels are probably associated with so-called vascular dementia as well … it is hard for doctors and researchers to distinguish between the two similar diagnoses.
Given what’s already known about the role of America’s “omega-imbalance” in promoting the inflammatory state proven to drive accumulation of arterial plaque, vascular disease, dementia, and obesity, the links between obesity, cholesterol, and dementia are probably the “smoke”, rather than the real fire underlying dementia.
For more on the overload of omega-6 fats in the American diet,and its effects on public health, see “New Report Finds Americans Need Far More Omega-3s” and search our newsletter archive for “omega-6”.
- 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 25.
- Corrada MM, Brookmeyer R, Berlau D, Paganini-Hill A, Kawas CH. Prevalence of dementia after age 90. Results from The 90+ Study.Neurology. 2008 Jul 2. [Epub ahead of print]
- Corrada MM, Kawas CH, Mozaffar F, Paganini-Hill A. Association of body mass index and weight change with all-cause mortality in the elderly. Am J Epidemiol. 2006 May 15;163(10):938-49. Epub 2006 Apr 26.
- Roberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF, Ivnik RJ, Tangalos EG, Petersen RC, Rocca WA. The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology. 2008;30(1):58-69. Epub 2008 Feb 7.
- Shinto L, Quinn J, Montine T, Baldauf-Wagner S, Bourdette D, Oken B, Kaye J. Omega-3 Fatty Acids and Lipoic Acid in Alzheimers Disease. Scientific Sessions: Aging and Dementia: Treatment. Thursday, April 17, 2008 2:45 PM. 60th Annual Meeting of the American Academy of Neurology, Saint Paul, MN, April 12-19, 2008. Accessed online July 26, 2008 at http://am.aan.com.
- Solomon A, Kivipelto M, Zhou J, Whitmer RA. Midlife Serum Total Cholesterol and Risk of Alzheimers Disease and Vascular Dementia Three Decades Later. Poster Sessions IV: Aging and Dementia: Risk Factors. Wednesday, April 16, 2008 7:00 AM. 60th Annual Meeting of the American Academy of Neurology, Saint Paul, MN, April 12-19, 2008. Accessed online July 26, 2008 at http://am.aan.com.
- Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ. Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br J Nutr. 2003 Apr;89(4):483-9.
- Wang W, Shinto L, Connor WE, Quinn JF. Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. J Alzheimers Dis. 2008 Feb;13(1):31-8.
- Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids. 2000 Dec;35(12):1305-12.
- Beydoun MA, Beydoun HA, Wang Y. Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev. 2008 May;9(3):204-18. Epub 2008 Mar 6. Erratum in: Obes Rev. 2008 May;9(3):267.